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Development of stereotypies and polydipsia in wild caught bank voles (Clethrionomys glareolus) and their laboratory-bred offspring.
Applied Animal Behaviour Science 68 Ž2000. 349–357 www.elsevier.comrlocaterapplanim
Development of stereotypies and polydipsia in wild caught bank voles žClethrionomys glareolus / and their laboratory-bred offspring. Is polydipsia a symptom of diabetes mellitus? B. Schoenecker ) , K.E. Heller, T. Freimanis Zoological Institute, UniÕersity of Copenhagen, TagensÕej 16, DK-2200 Copenhagen N, Denmark Accepted 31 January 2000
Abstract The development of stereotypies and polydipsia was studied in wild caught bank voles ŽP: n s 92. and their laboratory-bred offspring ŽF1: n s 248.. All animals were kept isolated in barren cages in the laboratory. In the P generation, no individuals developed stereotypies, but 22% developed polydipsia Ž) 21 mlrday water intake against normally 10 mlrday.. Polydipsia was more frequent among males Ž34%. than females Ž13%.. In F1, 30% developed locomotor stereotypies alone, 21% showed polydipsia alone, and, additionally, 7% developed both stereotypies and polydipsia. Fewer males than females developed stereotypies Ž23% vs. 38%., whereas polydipsia was more frequent in males than in females Ž30% vs. 11%.. The occurrence and distribution of polydipsia among sexes were the same in F1 and P. The distribution of different types of stereotypies in stereotyping voles were backward somersaulting ŽBS, 80%., high-speed jumping ŽJUMP, 29%., pacing following a fixed route ŽPF, 12%. and windscreen wiper movement ŽWIN, 5%.. Some individuals Ž10%. showed two or more different types of stereotypies. The average age for developing stereotypies was 96 days while polydipsia was registered at the age of 63 days in both sexes. Voles showing both polydipsia and stereotypies developed polydipsia later Ž79 days. than polydipsic voles not showing stereotypies. This difference was especially pronounced in stereotyping females in which the occurrence of polydipsia was postponed to the age of 114 days. Polydipsic voles were tested positive for glucosuria indicating
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Corresponding author. Tel.: q45-3532-1302; fax: q45-3532-1299. E-mail address: [email protected] ŽB. Schoenecker..
0168-1591r00r$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. PII: S 0 1 6 8 - 1 5 9 1 Ž 0 0 . 0 0 1 0 8 - 8
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B. Schoenecker et al.r Applied Animal BehaÕiour Science 68 (2000) 349–357
that polydipsia could be a symptom of diabetes mellitus. It is suggested that the development of stereotypies and polydipsia among bank voles in the laboratory are the results of frustration and prolonged stress. Stereotypies seem to depend on frustrative experiences early in life, while polydipsia may be related to diabetes mellitus caused by the experience of prolonged stress. Moreover, circumstances related to the development of stereotypies may be adaptive by reducing the risks of prolonged stress, including the development of fatal polydipsia. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Bank voles; Stereotypies; Polydipsia; Diabetes mellitus; Adaptive value
1. Introduction Stereotypies are the collective term for a group of phenotypic different behaviours that share the following three characteristics: Morphologically identical movements, ¨ which are repeated regularly and have no obvious function ŽOdberg, 1978.. Stereotypies occur in many different species kept in captivity or intensive husbandry and farms ŽMason, 1991.. Stressors like barren environments ŽSørensen, 1987., scheduled and restricted feeding ŽFalk, 1969, 1971; Bildsøe et al., 1991; Lawrence and Terlouw, 1993., social deprivation ŽSahakian et al., 1975; Broom, 1983; Arellano et al., 1992., frustration ¨ ¨ ŽFeldman, 1978; Odberg, 1978; Rushen, 1985; Odberg, 1987;. boredom ŽWemelsfelder, 1993. and tethering ŽCronin et al., 1985a. are generally associated with stereotypies. The eliciting circumstances, the ontogeny, and the context in which stereotypies are performed are very heterogenic ŽCronin et al., 1985b; Mason, 1991, 1993.. Laboratory-bred, but not wild caught, bank voles housed in barren cages develop spontaneous locomotor ¨ stereotypies with a high frequency ŽOdberg, 1986.. The voles perform easily recognisable stereotypies such as backward somersaulting ŽBS., jumping, pacing following a fixed route ŽPF. and windscreen wiper movement ŽWIN. ŽSørensen and Randrup, 1986; ¨ Odberg, 1986; Sørensen, 1987; Cooper and Nicol, 1991, 1996.. Increasing the size and complexity of the housing conditions reduces the incidence of stereotypies in bank voles ¨ ŽOdberg, 1987., but old voles show stronger perseverance of stereotypies than younger voles after environmental enrichment ŽCooper and Nicol, 1996.. Moreover, there seems to be no difference in mortality or fecundity between laboratory-bred and wild caught voles ŽCooper and Nicol, 1996.. Both wild caught and captivity-bred bank voles have been reported to develop excessive drinking or polydipsia in the laboratory ŽSørensen and Randrup, 1986., but the causes of this abnormality, its ontogeny and its relation to the occurrence of locomotor stereotypies is uncertain. Likewise, there is no detailed information on possible sex differences in the development of stereotypy and polydipsia, just as we know only a little about mortality especially in polydipsic voles. The present study aimed at examining the development of stereotypic behaviour and polydipsia in wild caught bank voles and their laboratory-bred offspring when kept isolated under barren housing conditions. Attention was specifically paid to associations with age and sex. Moreover, the possibility that polydipsia in bank voles could be a symptom of diabetes mellitus was preliminary tested ŽGanong, 1991..
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2. Materials and methods 2.1. Housing and breeding Wild bank voles Ž38 males and 54 females. representing the parental generation ŽP. were caught in August and September on the island Zealand, Denmark, using traditional live traps. The animals were transferred to small barren cages of transparent plastic Ž13.5 = 16.0 = 22.5 cm. and kept physically isolated in the laboratory under 12 h light conditions Ž0800–2000 h.. The cages were supplied with a woodcutting bed, and food Žstandard rat chow. and water were available ad libitum. Cage cleaning was performed every second week or when necessary. A portion of a grain mixture was given when the cages were cleaned. After an initial observation period of at least 5-week duration, single mating pairs were transferred to larger enriched cages Ž14.5 = 21.5 = 37.5 cm. supplied with a woodcutting bed, toilet paper, and paper rolls. The resultant offspring ŽF1. consisted of 138 males and 110 females in 52 different litters born from November to May. F1 individuals were weaned between the ages of 25 and 53 days and kept physically isolated for 180 days. 2.2. ObserÕations and classification One-zero sampling for 3–4 h everyday during the isolation period paid attention to stereotypic behaviour. When stereotypies were recognisable, the age and sex of the voles were noted along with the type of stereotypy performed. Mean daily water consumption was calculated for all animals. No attempts were made to estimate the amount of water not ingested. Voles were classified as stereotypers ŽS. if stereotypic behaviour were noted in bouts of at least five repetitions during the daily observation periods. These bouts, separated by small intervals, could continue for hours. The term S covered BS, high-speed jumping ŽJUMP., PF and WINs as previously defined ŽSørensen, 1987; Sørensen and ¨ Randrup, 1986; Odberg, 1986; Cooper and Nicol, 1991, 1996.. Voles were classified as polydipsic ŽPD. if their average daily water intake at least for a continuous month exceeded 21 ml Žcompared with 10 mlrday for average consumption.. Voles showing both PD and S were classified as polydipsic stereotypers ŽPDS.. Voles showing neither PD nor S were classified as wildtype ŽW.. Twenty polydipsic and 20 non-polydipsic voles were randomly selected and tested for glucosuria as a possible indication of diabetes mellitus ŽTESTAPE w , Eli Lilly and Company.. 2.3. Statistical analyses Data were tested for normality with Kolmogorov–Smirnov one-sample tests and F-tests for even variances. If data fulfilled the criteria needed for a parametric test, unpaired t-test and one-factor ANOVA were used. If not, data were treated with Kruskal–Wallis tests for general significance, followed by Mann–Whitney U-tests.
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Spearman rank correlation tests were used to estimate effects of isolation age on the age of development of stereotypies and polydipsia. Intersex differences in stereotypy frequencies and water consumption were tested with chi-square tests using Yates continuity correction factor. The same test was used on data from polydipsic and non-polydipsic voles with respect to glucosuria. The chosen significance level was 0.05 and the tests were two-tailed. Corrections for ties were performed if necessary.
3. Results 3.1. Stereotypies Table 1 illustrates the proportion Ž%. of animals in the four classifications ŽW, S, PD and PDS. in each of the two generations. No individuals in the P generation developed stereotypies, whereas stereotypic behaviour was observed in 37% F1 individuals ŽS q PDS.. There were no sex differences in the number of S q PDS animals, but significantly fewer males than females developed stereotypies alone ŽS. Ž P - 0.05.. Approximately 10% of the F1 animals developed two or more different types of stereotypies. The distribution of different types of stereotypies in F1 is depicted in Fig. 1. The preferred stereotypy was BS Ž P - 0.0001.. JUMP was preferred over PF Ž P - 0.01. and WIN Ž P - 0.0001., and no sex differences were shown in stereotypy distribution. Table 2 shows the age at which the F1 voles were classified as S, PD and PDS. Stereotypies were developed at the age of 96 days for both sexes. Comparisons of the two most common types of stereotypies showed that JUMP appeared earlier Ž60 days. than BS Ž105 days. Ž P - 0.0001.. There were no relationships between the age at isolation and age at which stereotypies were observed, and there were no effects of isolation age on the number of stereotyping voles.
Table 1 Proportion Ž%. of male and female voles classified as stereotypers ŽS., polydipsic ŽPD. and as both stereotypers and polydipsic ŽPDS. in P and F1 ClassificationrGeneration
W
S
PD
PDS
PDqPDS
P (%) Males Ž ns 38. Females Ž ns 54. Malesqfemales
66 87 ) 78
0 0 0
34 13 ) 22
0 0 0
34 13 ) 22
F1 % Males Ž ns138. Females Ž ns110. Malesqfemales
38 46 ) 42
23 38 ) 30
30 11) ) ) 21
9 6 7
38 16 ) ) ) 29
)
P - 0.05. P - 0.001.
)))
SqPDS 0 0 0
32 44 37
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Fig. 1. Proportions Ž%. of male and female voles showing different types of stereotypies. The total exceeds 100% because some voles showed two or more stereotypies. Abbreviations as in text.
3.2. Polydipsia There were no significant differences between the occurrence of polydipsia ŽPD q PDS. in P Ž22%. and F1 Ž29%., but the proportion of polydipsic males was more than twice the proportion of polydipsic females in both generations ŽP: P - 0.05; F1: P - 0.001. ŽTable 1.. Daily water consumption in male and female W voles was 9.8 and 9.0 mlrday, respectively. S males drank 9.2 mlrday and S females reached 10.3 mlrday Ž P - 0.05 compared with W females.. PD males drank 67.0 mlrday and PD females reached 60.8 mlrday, while PDS males and females drank 65.6 mlrday and 50.7 mlrday, respectively. There was no sex effect on water consumption. There was no sex difference in age for showing polydipsia, but polydipsia was developed later than stereotypies in males Ž60 vs. 99 days, P - 0.001. ŽTable 2.. There
Table 2 Average age in days for the occurrence of stereotypies ŽS. and polydipsia ŽPD. PDS-S and PDS-PD indicate age for classification as S and PD in voles showing both stereotypies and polydipsia. Differences between different classifications are shown below. Day of observation
S
PD
PDS-S
PDS-PD
F1 Males Ž ns85. Females Ž ns60. Malesqfemales
99 94 96
60 74 63
86 90 87
62 114 ) 79
Day of observation
Males
Females
Malesqfemales
S vs. PD S vs PDS-S S vs. PDS-PD PD vs. PDS-S PD vs. PDS-PD PDS-S vs. PDS-PD
)) )
NS NS NS NS
)))
NS
)
)
NS
NS NS
)
P - 0.05. P - 0.01. ))) P - 0.001. ))
NS )) )) )
NS ) )))
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Table 3 Proportion of polydipsic and non-polydipsic voles tested positive and negative for glucosuria Glucosuria %
Positive
Negative
Polydipsic Ž ns 20. Non-polydipsic Ž ns 20.
65 0)))
35 100
)))
P - 0.001.
were no effects of isolation age on the number of voles developing polydipsia, the time for polydipsia to occur or the amount of water consumed. 3.3. Stereotypies and polydipsia Approximately 7% F1 voles were classified as PDS ŽTable 1. with no significant difference related to sex. PDS animals developed polydipsia later Ž79 days. than PD animals Ž63 days., and this was especially pronounced in females Ž114 vs. 74 days, P - 0.05. ŽTable 2.. Comparisons between all non-stereotyping voles ŽW q PD, n s 156. and all stereotyping voles ŽS q PDS, n s 92. showed that polydipsia occurred most frequently in non-stereotypers ŽW q PD: 34%; S q PDS: 20%, P - 0.05.. 3.4. Polydipsia and glucosuria Table 3 shows the proportion Ž%. of voles tested positive for glucosuria. None of the non-polydipsic voles were tested positive, whereas 65% polydipsic voles showed clear signs of glucosuria Ž P - 0.001..
4. Discussion The present study repeats the previous findings that laboratory-bred, but not wild ¨ caught voles, easily develop stereotypies under barren housing conditions ŽOdberg, 1986; Sørensen, 1987; Sørensen and Randrup, 1986; Cooper and Nicol, 1991, 1996.. Moreover, it demonstrates that males are more disposed to develop stereotypies than females, whereas there are no sex differences in the types of stereotypies shown. BS is the most commonly observed stereotypy in our Danish voles and this is in contrast to the finding of JUMP being the preferred stereotypy in laboratory-bred voles originating from geographically different populations ŽSørensen, 1987.. Thus, it appears that strain or population differences relate to the types of stereotypies preferably developed in the ¨ Ž1987. recorded jumping stereotypies before the age of 30 days in laboratory. Odberg voles, and Cooper and Nicol Ž1991. report that stereotypies in laboratory-bred voles develop when the animals are 4 months old. Apart from possible strain or population differences, estimates of the occurrence of stereotypies depend on the definition of stereotypy employed, and especially on the exact time course Žduration and frequency.
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that the behaviour has to fulfil in order to be classified as a stereotypy. It cannot be ignored, however, that management and handling of the laboratory-bred voles play a role for the type of stereotypies developed. When cleaning the cages in the present study, it was necessary to transfer the animals from their home cages with old woodcut bedding to cages with new bedding material. During this procedure, young voles responded almost immediately by showing non-stereotyped jumping movements in the cage corners or against the cage walls in both old and new cages. Non-stereotyping older voles responded with digging in the new bedding material while stereotyping voles exhibited their preferred stereotypy. The jumping responses of the young voles occurred in the breeding cages as well as after isolation. Non-stereotyped jumping in young voles may be interpreted as unsuccessful attempts to escape during disturbance, and the lack of a successful outcome of an otherwise adequate escape response could be the source of ¨ subsequent stereotypic behaviour Žas also suggested by Odberg, 1986.. If so, stereotypic behaviour already developed may be elicited at least partially by the same circumstances that originally caused their development, but in addition that, stereotypies may also occur in other contexts. It could be that these other contexts share the common frustrating feature of unsuccessful results of otherwise adequate behavioural responses such as frustrating effects of social deprivation. The lack of stereotypy development in wild caught voles may thus relate to the lack of such frustrating experiences among young voles in the wild. This interpretation is partially supported by the finding that environmental enrichment of the cage milieu reduces the perseverance of stereotypies in young but not to the same extent in old laboratory-bred voles ŽCooper et al., 1996.. The development of spontaneous polydipsia in both wild caught and laboratory-bred voles is difficult to interpret. We assume that polydipsia due to its association with high mortality ŽSørensen and Randrup, 1986. is rare in the wild. Polydipsia has been observed as a result of diabetes mellitus induced by prolonged glucocorticoid treatment, exposure to toxins, viral infections, surgical lesions and other presumable stressful influences ŽCraighead, 1975; Hunt et al., 1976; Mormedes and Rossini, 1981; Schlosser et al., 1984; Tarui et al., 1987; Goodwin, 1991.. In the present study, polydipsia was clearly associated with glucosuria. It is therefore possible that keeping voles isolated under barren conditions in the laboratory represents a stressful experience for the animals leading to diabetes and excessive drinking. Modifying temporal reward patterns under experimental learning conditions can also provoke excessive drinking in rodents ŽSchedule Induced Polydipsia or SIP. and this experimentally induced response is frequently used as an animal model for human mental disorders Že.g. Woods et al., 1993; Roerh et al., 1995.. Polydipsia is a characteristic feature of chronic schizophrenic humans, but although some psychopharmaca effectively reduce spontaneous polydipsia in psychiatric patients ŽFuller et al., 1996; Spears et al., 1996; Verghese et al., 1996., provoked SIP in rodents may be left unaffected by similar treatments ŽRoerh et al., 1995.. Referring to the above-mentioned possible frustrating or stress-related feature of keeping voles isolated under barren conditions, the occurrence of polydipsia in the present study may very well parallel the condition of SIP, which also seems associated with frustration. Combinations of causes may also explain polydipsia development, but the validity of the interpretations presented here will have to await further and more specific studies.
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The same holds true for explaining why males seem more prone to develop polydipsia than females, while no major sex differences were found in the tendency to develop stereotypies. One possibility is, of course, that both sexes experience frustration under the laboratory conditions leading to stereotypies, but that males are more easily brought to a state of prolonged stress, and for that reason, more easily develop the pathologic state of polydipsia and perhaps diabetes mellitus. Based on the present findings, the development of stereotypies appears to mitigate the development of polydipsia in both sexes. Very few individuals developed both stereotypies and polydipsia, but among these few, polydipsia occurred later than in voles developing polydipsia alone. In conclusion, we suggest that the development of stereotypies and polydipsia among bank voles in the laboratory are the results of frustration and prolonged stress. Stereotypies seem to depend on frustrative experiences early in life, while polydipsia may be related to diabetes mellitus caused by the experience of prolonged stress. Moreover, circumstances related to the development of stereotypies may have an adaptive value by reducing the risks of prolonged stress, including the development of fatal polydipsia.
Acknowledgements The Danish Natural Science Research Council supported this study.
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Feldman, R.S., 1978. Environmental and physiological determinants of fixated behaviour in mammals. In: Carsi ŽEd.., Proc. 1st World Congress on Ethology Applied to Zoo-technics Vol. 1 Madrid Industrias graficas Espagna, pp. 487–493. Fuller, M.A., Jurjus, G., Kwon, K., Konicki, P.E., Jaskiw, G.E., 1996. Clozapine reduces water-drinking behavior in schizophrenic patients with polydipsia. J. Clin. Psychopharmacol. 16 Ž4., 329–332. Ganong, W.F., 1991. Review of Medical Physiology. 15th edn. Appleton and Lange, Prentice-Hall, London, UK. Goodwin, J.S., 1991. In: Sites, D.P., Terr, A.I. ŽEds.., Basic and Clinical Immunology. 7th edn. Lange Medical Books, pp. 787–794. Hunt, C.E., Lindsey, J.R., Walkley, S.U., 1976. Animal models of diabetes and obesity, including the PBBrld mouse. Fed. Proc. 35 Ž5., 1206–1217. Lawrence, A.B., Terlouw, E.M.C., 1993. A review of behavioral factors involved in the development and continued performance of stereotypic behaviors in pigs. J. Anim. Sci. 71 Ž10., 2815–2825. Mason, G.J., 1991. Stereotypies: a critical review. Anim. Behav. 41, 1015–1037. Mason, G.J., 1993. Forms of stereotypic behaviour. In: Lawrence, A.B., Rushen, J. ŽEds.., Stereotypic Animal Behaviour: Fundamentals and Applications to Welfare. C.A.B.I., Wallingford, UK, pp. 7–40. Mormedes, J.P., Rossini, A.A., 1981. Animal models of diabetes. Am. J. Med. 70, 353–360. ¨ Odberg, F.O., 1978. Abnormal behaviours: stereotypies. In: Carsi ŽEd.., Proc. 1st World Congress on Ethology Applied to Zoo-technics vol. 1 Madrid Industrias graficas Espagna, pp. 475–480. ¨ Odberg, F.O., 1986. The jumping stereotypy in the bank vole Ž Clethrionomys glareolus .. Biol. Behav. 11, 130–143. ¨ Odberg, F.O., 1987. Behavioral responses to stress in farm animals. In: Wiepkema, P.R., van Adrichem, P.W.M. ŽEds.., Biology of Stress in Farm Animals: An Integrative Approach. Martinus Nijhoff, Dordrecht, pp. 135–150. Roerh, J., Woods, A., Corbett, R., Kongsamut, S., 1995. Changes in paroxetine binding in the cerebral cortex of polydipsic rats. Eur. J. Pharmacol. 278, 75–78. Rushen, J.P., 1985. Stereotypies, aggression and the feeding schedules of tethered sows. Appl. Anim. Behav. Sci. 14, 137–147. Sahakian, B.J., Robbins, T.W., Morgan, M.J., Iversen, S.D., 1975. The effects of psychomotor stimulants on stereotypy and locomotor activity in socially-deprived and control rats. Brain Res. 84, 195–205. Spears, N.M., Leadbetter, R.A., Shutty, M.S., 1996. Clozapine treatment in polydipsia and intermittent hyponatremia. J. Clin. Psychiatry 57 Ž3., 123–128. Sørensen, G., 1987. Stereotyped behaviour, hyperaggressiveness and ‘‘tyrannic’’ hierachy induced in bank voles Ž Clethrionomys glareolus . by a restricted cage milieu. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 11, 9–21. Sørensen, G., Randrup, A., 1986. Possible protective value of severe psychopathology against lethal effects of an unfavourable milieu. Stress Med. 2, 103–105. Tarui, S., Yamada, K., Hanafusa, T., 1987. Animal models utilized in the research of diabetes mellitus with special reference to insulitis-associated diabets. Prog. Clin. Biol. Res. 229, 211–223. Verghese, C., deLeon, J., Josiassen, R.C., 1996. Problems and progress in the diagnosis and treatment of polydipsia and hyponatremia. Schizophr. Bull. 22 Ž3., 709–713. Wemelsfelder, F., 1993. The concept of animal boredom and its relationship to stereotyped behaviour. In: Lawrence, A.B., Rushen, J. ŽEds.., Stereotypic Animal Behaviour: Fundamental and Applications to Welfare. C.A.B.I., Wallingford, UK, pp. 65–95. Woods, A., Smith, C., Szewczak, M., Dunn, R.W., Cornfeldt, M., Corbett, R., 1993. Selective serotonin re-uptake inhibitors decrease schedule-induced polydipsia in rats: a potential model for obsessive compulsive disorder. Psychopharmacology 112, 195–198.
Development of stereotypies and polydipsia in wild caught bank voles žClethrionomys glareolus / and their laboratory-bred offspring. Is polydipsia a symptom of diabetes mellitus? B. Schoenecker ) , K.E. Heller, T. Freimanis Zoological Institute, UniÕersity of Copenhagen, TagensÕej 16, DK-2200 Copenhagen N, Denmark Accepted 31 January 2000
Abstract The development of stereotypies and polydipsia was studied in wild caught bank voles ŽP: n s 92. and their laboratory-bred offspring ŽF1: n s 248.. All animals were kept isolated in barren cages in the laboratory. In the P generation, no individuals developed stereotypies, but 22% developed polydipsia Ž) 21 mlrday water intake against normally 10 mlrday.. Polydipsia was more frequent among males Ž34%. than females Ž13%.. In F1, 30% developed locomotor stereotypies alone, 21% showed polydipsia alone, and, additionally, 7% developed both stereotypies and polydipsia. Fewer males than females developed stereotypies Ž23% vs. 38%., whereas polydipsia was more frequent in males than in females Ž30% vs. 11%.. The occurrence and distribution of polydipsia among sexes were the same in F1 and P. The distribution of different types of stereotypies in stereotyping voles were backward somersaulting ŽBS, 80%., high-speed jumping ŽJUMP, 29%., pacing following a fixed route ŽPF, 12%. and windscreen wiper movement ŽWIN, 5%.. Some individuals Ž10%. showed two or more different types of stereotypies. The average age for developing stereotypies was 96 days while polydipsia was registered at the age of 63 days in both sexes. Voles showing both polydipsia and stereotypies developed polydipsia later Ž79 days. than polydipsic voles not showing stereotypies. This difference was especially pronounced in stereotyping females in which the occurrence of polydipsia was postponed to the age of 114 days. Polydipsic voles were tested positive for glucosuria indicating
)
Corresponding author. Tel.: q45-3532-1302; fax: q45-3532-1299. E-mail address: [email protected] ŽB. Schoenecker..
0168-1591r00r$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. PII: S 0 1 6 8 - 1 5 9 1 Ž 0 0 . 0 0 1 0 8 - 8
350
B. Schoenecker et al.r Applied Animal BehaÕiour Science 68 (2000) 349–357
that polydipsia could be a symptom of diabetes mellitus. It is suggested that the development of stereotypies and polydipsia among bank voles in the laboratory are the results of frustration and prolonged stress. Stereotypies seem to depend on frustrative experiences early in life, while polydipsia may be related to diabetes mellitus caused by the experience of prolonged stress. Moreover, circumstances related to the development of stereotypies may be adaptive by reducing the risks of prolonged stress, including the development of fatal polydipsia. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Bank voles; Stereotypies; Polydipsia; Diabetes mellitus; Adaptive value
1. Introduction Stereotypies are the collective term for a group of phenotypic different behaviours that share the following three characteristics: Morphologically identical movements, ¨ which are repeated regularly and have no obvious function ŽOdberg, 1978.. Stereotypies occur in many different species kept in captivity or intensive husbandry and farms ŽMason, 1991.. Stressors like barren environments ŽSørensen, 1987., scheduled and restricted feeding ŽFalk, 1969, 1971; Bildsøe et al., 1991; Lawrence and Terlouw, 1993., social deprivation ŽSahakian et al., 1975; Broom, 1983; Arellano et al., 1992., frustration ¨ ¨ ŽFeldman, 1978; Odberg, 1978; Rushen, 1985; Odberg, 1987;. boredom ŽWemelsfelder, 1993. and tethering ŽCronin et al., 1985a. are generally associated with stereotypies. The eliciting circumstances, the ontogeny, and the context in which stereotypies are performed are very heterogenic ŽCronin et al., 1985b; Mason, 1991, 1993.. Laboratory-bred, but not wild caught, bank voles housed in barren cages develop spontaneous locomotor ¨ stereotypies with a high frequency ŽOdberg, 1986.. The voles perform easily recognisable stereotypies such as backward somersaulting ŽBS., jumping, pacing following a fixed route ŽPF. and windscreen wiper movement ŽWIN. ŽSørensen and Randrup, 1986; ¨ Odberg, 1986; Sørensen, 1987; Cooper and Nicol, 1991, 1996.. Increasing the size and complexity of the housing conditions reduces the incidence of stereotypies in bank voles ¨ ŽOdberg, 1987., but old voles show stronger perseverance of stereotypies than younger voles after environmental enrichment ŽCooper and Nicol, 1996.. Moreover, there seems to be no difference in mortality or fecundity between laboratory-bred and wild caught voles ŽCooper and Nicol, 1996.. Both wild caught and captivity-bred bank voles have been reported to develop excessive drinking or polydipsia in the laboratory ŽSørensen and Randrup, 1986., but the causes of this abnormality, its ontogeny and its relation to the occurrence of locomotor stereotypies is uncertain. Likewise, there is no detailed information on possible sex differences in the development of stereotypy and polydipsia, just as we know only a little about mortality especially in polydipsic voles. The present study aimed at examining the development of stereotypic behaviour and polydipsia in wild caught bank voles and their laboratory-bred offspring when kept isolated under barren housing conditions. Attention was specifically paid to associations with age and sex. Moreover, the possibility that polydipsia in bank voles could be a symptom of diabetes mellitus was preliminary tested ŽGanong, 1991..
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2. Materials and methods 2.1. Housing and breeding Wild bank voles Ž38 males and 54 females. representing the parental generation ŽP. were caught in August and September on the island Zealand, Denmark, using traditional live traps. The animals were transferred to small barren cages of transparent plastic Ž13.5 = 16.0 = 22.5 cm. and kept physically isolated in the laboratory under 12 h light conditions Ž0800–2000 h.. The cages were supplied with a woodcutting bed, and food Žstandard rat chow. and water were available ad libitum. Cage cleaning was performed every second week or when necessary. A portion of a grain mixture was given when the cages were cleaned. After an initial observation period of at least 5-week duration, single mating pairs were transferred to larger enriched cages Ž14.5 = 21.5 = 37.5 cm. supplied with a woodcutting bed, toilet paper, and paper rolls. The resultant offspring ŽF1. consisted of 138 males and 110 females in 52 different litters born from November to May. F1 individuals were weaned between the ages of 25 and 53 days and kept physically isolated for 180 days. 2.2. ObserÕations and classification One-zero sampling for 3–4 h everyday during the isolation period paid attention to stereotypic behaviour. When stereotypies were recognisable, the age and sex of the voles were noted along with the type of stereotypy performed. Mean daily water consumption was calculated for all animals. No attempts were made to estimate the amount of water not ingested. Voles were classified as stereotypers ŽS. if stereotypic behaviour were noted in bouts of at least five repetitions during the daily observation periods. These bouts, separated by small intervals, could continue for hours. The term S covered BS, high-speed jumping ŽJUMP., PF and WINs as previously defined ŽSørensen, 1987; Sørensen and ¨ Randrup, 1986; Odberg, 1986; Cooper and Nicol, 1991, 1996.. Voles were classified as polydipsic ŽPD. if their average daily water intake at least for a continuous month exceeded 21 ml Žcompared with 10 mlrday for average consumption.. Voles showing both PD and S were classified as polydipsic stereotypers ŽPDS.. Voles showing neither PD nor S were classified as wildtype ŽW.. Twenty polydipsic and 20 non-polydipsic voles were randomly selected and tested for glucosuria as a possible indication of diabetes mellitus ŽTESTAPE w , Eli Lilly and Company.. 2.3. Statistical analyses Data were tested for normality with Kolmogorov–Smirnov one-sample tests and F-tests for even variances. If data fulfilled the criteria needed for a parametric test, unpaired t-test and one-factor ANOVA were used. If not, data were treated with Kruskal–Wallis tests for general significance, followed by Mann–Whitney U-tests.
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Spearman rank correlation tests were used to estimate effects of isolation age on the age of development of stereotypies and polydipsia. Intersex differences in stereotypy frequencies and water consumption were tested with chi-square tests using Yates continuity correction factor. The same test was used on data from polydipsic and non-polydipsic voles with respect to glucosuria. The chosen significance level was 0.05 and the tests were two-tailed. Corrections for ties were performed if necessary.
3. Results 3.1. Stereotypies Table 1 illustrates the proportion Ž%. of animals in the four classifications ŽW, S, PD and PDS. in each of the two generations. No individuals in the P generation developed stereotypies, whereas stereotypic behaviour was observed in 37% F1 individuals ŽS q PDS.. There were no sex differences in the number of S q PDS animals, but significantly fewer males than females developed stereotypies alone ŽS. Ž P - 0.05.. Approximately 10% of the F1 animals developed two or more different types of stereotypies. The distribution of different types of stereotypies in F1 is depicted in Fig. 1. The preferred stereotypy was BS Ž P - 0.0001.. JUMP was preferred over PF Ž P - 0.01. and WIN Ž P - 0.0001., and no sex differences were shown in stereotypy distribution. Table 2 shows the age at which the F1 voles were classified as S, PD and PDS. Stereotypies were developed at the age of 96 days for both sexes. Comparisons of the two most common types of stereotypies showed that JUMP appeared earlier Ž60 days. than BS Ž105 days. Ž P - 0.0001.. There were no relationships between the age at isolation and age at which stereotypies were observed, and there were no effects of isolation age on the number of stereotyping voles.
Table 1 Proportion Ž%. of male and female voles classified as stereotypers ŽS., polydipsic ŽPD. and as both stereotypers and polydipsic ŽPDS. in P and F1 ClassificationrGeneration
W
S
PD
PDS
PDqPDS
P (%) Males Ž ns 38. Females Ž ns 54. Malesqfemales
66 87 ) 78
0 0 0
34 13 ) 22
0 0 0
34 13 ) 22
F1 % Males Ž ns138. Females Ž ns110. Malesqfemales
38 46 ) 42
23 38 ) 30
30 11) ) ) 21
9 6 7
38 16 ) ) ) 29
)
P - 0.05. P - 0.001.
)))
SqPDS 0 0 0
32 44 37
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Fig. 1. Proportions Ž%. of male and female voles showing different types of stereotypies. The total exceeds 100% because some voles showed two or more stereotypies. Abbreviations as in text.
3.2. Polydipsia There were no significant differences between the occurrence of polydipsia ŽPD q PDS. in P Ž22%. and F1 Ž29%., but the proportion of polydipsic males was more than twice the proportion of polydipsic females in both generations ŽP: P - 0.05; F1: P - 0.001. ŽTable 1.. Daily water consumption in male and female W voles was 9.8 and 9.0 mlrday, respectively. S males drank 9.2 mlrday and S females reached 10.3 mlrday Ž P - 0.05 compared with W females.. PD males drank 67.0 mlrday and PD females reached 60.8 mlrday, while PDS males and females drank 65.6 mlrday and 50.7 mlrday, respectively. There was no sex effect on water consumption. There was no sex difference in age for showing polydipsia, but polydipsia was developed later than stereotypies in males Ž60 vs. 99 days, P - 0.001. ŽTable 2.. There
Table 2 Average age in days for the occurrence of stereotypies ŽS. and polydipsia ŽPD. PDS-S and PDS-PD indicate age for classification as S and PD in voles showing both stereotypies and polydipsia. Differences between different classifications are shown below. Day of observation
S
PD
PDS-S
PDS-PD
F1 Males Ž ns85. Females Ž ns60. Malesqfemales
99 94 96
60 74 63
86 90 87
62 114 ) 79
Day of observation
Males
Females
Malesqfemales
S vs. PD S vs PDS-S S vs. PDS-PD PD vs. PDS-S PD vs. PDS-PD PDS-S vs. PDS-PD
)) )
NS NS NS NS
)))
NS
)
)
NS
NS NS
)
P - 0.05. P - 0.01. ))) P - 0.001. ))
NS )) )) )
NS ) )))
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Table 3 Proportion of polydipsic and non-polydipsic voles tested positive and negative for glucosuria Glucosuria %
Positive
Negative
Polydipsic Ž ns 20. Non-polydipsic Ž ns 20.
65 0)))
35 100
)))
P - 0.001.
were no effects of isolation age on the number of voles developing polydipsia, the time for polydipsia to occur or the amount of water consumed. 3.3. Stereotypies and polydipsia Approximately 7% F1 voles were classified as PDS ŽTable 1. with no significant difference related to sex. PDS animals developed polydipsia later Ž79 days. than PD animals Ž63 days., and this was especially pronounced in females Ž114 vs. 74 days, P - 0.05. ŽTable 2.. Comparisons between all non-stereotyping voles ŽW q PD, n s 156. and all stereotyping voles ŽS q PDS, n s 92. showed that polydipsia occurred most frequently in non-stereotypers ŽW q PD: 34%; S q PDS: 20%, P - 0.05.. 3.4. Polydipsia and glucosuria Table 3 shows the proportion Ž%. of voles tested positive for glucosuria. None of the non-polydipsic voles were tested positive, whereas 65% polydipsic voles showed clear signs of glucosuria Ž P - 0.001..
4. Discussion The present study repeats the previous findings that laboratory-bred, but not wild ¨ caught voles, easily develop stereotypies under barren housing conditions ŽOdberg, 1986; Sørensen, 1987; Sørensen and Randrup, 1986; Cooper and Nicol, 1991, 1996.. Moreover, it demonstrates that males are more disposed to develop stereotypies than females, whereas there are no sex differences in the types of stereotypies shown. BS is the most commonly observed stereotypy in our Danish voles and this is in contrast to the finding of JUMP being the preferred stereotypy in laboratory-bred voles originating from geographically different populations ŽSørensen, 1987.. Thus, it appears that strain or population differences relate to the types of stereotypies preferably developed in the ¨ Ž1987. recorded jumping stereotypies before the age of 30 days in laboratory. Odberg voles, and Cooper and Nicol Ž1991. report that stereotypies in laboratory-bred voles develop when the animals are 4 months old. Apart from possible strain or population differences, estimates of the occurrence of stereotypies depend on the definition of stereotypy employed, and especially on the exact time course Žduration and frequency.
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that the behaviour has to fulfil in order to be classified as a stereotypy. It cannot be ignored, however, that management and handling of the laboratory-bred voles play a role for the type of stereotypies developed. When cleaning the cages in the present study, it was necessary to transfer the animals from their home cages with old woodcut bedding to cages with new bedding material. During this procedure, young voles responded almost immediately by showing non-stereotyped jumping movements in the cage corners or against the cage walls in both old and new cages. Non-stereotyping older voles responded with digging in the new bedding material while stereotyping voles exhibited their preferred stereotypy. The jumping responses of the young voles occurred in the breeding cages as well as after isolation. Non-stereotyped jumping in young voles may be interpreted as unsuccessful attempts to escape during disturbance, and the lack of a successful outcome of an otherwise adequate escape response could be the source of ¨ subsequent stereotypic behaviour Žas also suggested by Odberg, 1986.. If so, stereotypic behaviour already developed may be elicited at least partially by the same circumstances that originally caused their development, but in addition that, stereotypies may also occur in other contexts. It could be that these other contexts share the common frustrating feature of unsuccessful results of otherwise adequate behavioural responses such as frustrating effects of social deprivation. The lack of stereotypy development in wild caught voles may thus relate to the lack of such frustrating experiences among young voles in the wild. This interpretation is partially supported by the finding that environmental enrichment of the cage milieu reduces the perseverance of stereotypies in young but not to the same extent in old laboratory-bred voles ŽCooper et al., 1996.. The development of spontaneous polydipsia in both wild caught and laboratory-bred voles is difficult to interpret. We assume that polydipsia due to its association with high mortality ŽSørensen and Randrup, 1986. is rare in the wild. Polydipsia has been observed as a result of diabetes mellitus induced by prolonged glucocorticoid treatment, exposure to toxins, viral infections, surgical lesions and other presumable stressful influences ŽCraighead, 1975; Hunt et al., 1976; Mormedes and Rossini, 1981; Schlosser et al., 1984; Tarui et al., 1987; Goodwin, 1991.. In the present study, polydipsia was clearly associated with glucosuria. It is therefore possible that keeping voles isolated under barren conditions in the laboratory represents a stressful experience for the animals leading to diabetes and excessive drinking. Modifying temporal reward patterns under experimental learning conditions can also provoke excessive drinking in rodents ŽSchedule Induced Polydipsia or SIP. and this experimentally induced response is frequently used as an animal model for human mental disorders Že.g. Woods et al., 1993; Roerh et al., 1995.. Polydipsia is a characteristic feature of chronic schizophrenic humans, but although some psychopharmaca effectively reduce spontaneous polydipsia in psychiatric patients ŽFuller et al., 1996; Spears et al., 1996; Verghese et al., 1996., provoked SIP in rodents may be left unaffected by similar treatments ŽRoerh et al., 1995.. Referring to the above-mentioned possible frustrating or stress-related feature of keeping voles isolated under barren conditions, the occurrence of polydipsia in the present study may very well parallel the condition of SIP, which also seems associated with frustration. Combinations of causes may also explain polydipsia development, but the validity of the interpretations presented here will have to await further and more specific studies.
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The same holds true for explaining why males seem more prone to develop polydipsia than females, while no major sex differences were found in the tendency to develop stereotypies. One possibility is, of course, that both sexes experience frustration under the laboratory conditions leading to stereotypies, but that males are more easily brought to a state of prolonged stress, and for that reason, more easily develop the pathologic state of polydipsia and perhaps diabetes mellitus. Based on the present findings, the development of stereotypies appears to mitigate the development of polydipsia in both sexes. Very few individuals developed both stereotypies and polydipsia, but among these few, polydipsia occurred later than in voles developing polydipsia alone. In conclusion, we suggest that the development of stereotypies and polydipsia among bank voles in the laboratory are the results of frustration and prolonged stress. Stereotypies seem to depend on frustrative experiences early in life, while polydipsia may be related to diabetes mellitus caused by the experience of prolonged stress. Moreover, circumstances related to the development of stereotypies may have an adaptive value by reducing the risks of prolonged stress, including the development of fatal polydipsia.
Acknowledgements The Danish Natural Science Research Council supported this study.
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