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Reduction of neophobia in mice following lesions of the caudate-putamen
Physiology & Behavior, Vol. 36, pp. 25--28.Copyright©PergamonPress Ltd., 1986.Printedin the U.S.A.
0031-9384/86$3.00 + .00
Reduction of Neophobia in Mice Following Lesions of the Caudate-Putamen MARC CIGRANG, ELISE VOGEL AND RENE MISSLIN
Laboratoire de Psychophysiologie, 7 rue de l' Universitd F-67000 Strasbourg R e c e i v e d 12 O c t o b e r 1984 CIGRANG, M., E. VOGEL AND R. MISSLIN. Reduction of neophobia in mice following lesions of the caudateputamen. PHYSIOL BEHAV 36(1) 25-28, 1986. --Electrolytic lesions of the caudate-putamen result in a significant decrease in neophobic responses in mice towards a novel object introduced into their familiar environment; however, preference for a novel environment was not altered by the lesion. These data provide a parallel between the effects of lesions of the caudate-putamen and the well-known "amygdala-lesion-syndrome." It is suggested that the striatal complex, which receives massive afferent projection systems, plays a crucial role in sensory-motor integration processes which allow the animals to adapt their responses towards biological significant stimuli in order to cope with their environment. Putamen
Neophobia
Mice
Striatal complex
METHOD
THE striatal complex (caudate-putamen, nucleus accumbens and olfactory tubercle) is traditionally considered to be primarily motoric in function (tonic and postural regulation, initiation and smooth execution of movement). However, the anatomy of the afferent and efferent striatal projections [6,10] and recent behavioral data [8, 9, 12, 18] suggest that the striatum might be able to affect the initiation of goal directed behaviors such as responses to novelty in the environment. The term " n e o t i c " behavior has been used to describe the entire range of responses to novel stimuli including exploration, neophobia, aggression and orientation [4]. For example, a novel object introduced in a familiar environment induces avoidance and burying responses (neophobia) in rats [1] and in mice [13]. Other authors demonstrated that rats [16, 17, 20], mice [19] and Mongolian gerbils [5] shocked once by a prod buried the shock prod with bedding material. When given the opportunity to freely move around in simultaneously presented novel and familiar environments for 10 min, rats or mice spend a greater amount of time in the novel compartment (novelty preference) [7,15]. However, in this latter situation, mice first display avoidance reactions and neophobia towards a novel environment before showing a significant preference for it. Bilateral electrolytic lesions of lateral and basolateral amygdaloid nuclei in mice produce a lack of defensive responses towards novel stimuli, but do not affect their neotic preference [ 15]. Blanchard, Blanchard, Lee and Williams [3] reported that lesions in various portions of the striatum of wild rats sharply reduced the defensiveness of these animals to nonpainful stimuli. It is hypothesized that the striatal complex and its connections are important in sensori-motor integration, playing the role of an interface between the limbic system (mediating affect) and motor outputs. The present investigation attempts to study the behavioral effects of electrolytic lesions in the caudate-putamen on several neotic responses in mice.
Animals Forty adult male Swiss albino mice from our laboratory, 8 weeks of age at the time of testing, were used. Prior to experimental training, they were housed five in a standard cage containing a constant supply of food pellets and water, and kept on a 12/12 light/dark cycle with lights on at 1 a.m. They were randomly divided into two groups of 20 each. One group received bilateral electrolytic lesions of the caudateputamen, while the other served as sham-operated controls.
Surgery All subjects were operated under clean but not aseptic conditions, using sodium pentobarbital anesthesia (50 mg/kg). With the skull horizontal between bregma and lambda and using lambda as a landmark, electrodes were stereotaxically lowered to the caudate-putamen and the lesions were made electrolyticaily with an anodal current of 2 mA for a 15 sec duration. Two discrete bilateral lesions were placed in the putamen at +4.5 mm anterior to the lambda, +2 mm lateral from the midline and - 4 . 5 mm below the surface of the skull. The sham-operated subjects received the same treatment, except that the current was not delivered. After surgery, mice were immediately returned to their cage.
Apparatus The apparatus consisted of a polyvinyl chloride box (30 × 20× 20 cm), subdivided into six equal square exploratory units, all communicating by small doors, and covered with Plexiglas. It could be divided into half lengthwise by three movable doors so that the middle openings could be opened or closed. The apparatus was kept on a stand in the room which housed the mice. During observations, the experimenter, who was ignorant of the animal's treatment, always stood next to the box at the same place.
25
26
CIGRANG, VOGEL AND MISSLIN
I00
tu w it_
Ii.
50
lml
Lesioned
(
/
0 Z
/
•
/
s
!o
~
o°, ~ ,
,i
L
"~,,/'
Minutes
FIG. 1. Mean percentages of the novelty preference in caudateputamen lesioned mice (L) and sham-lesioned controls (C). Arrows show the moment after which mice displayed a significant preference for the novel compartment (sign test).
FIG. 2. The locus and extent of the damage in the caudate-putamen. cc=Corpus callosum, ca=commissura anterior, cd=nucleus caudatus, gp=globus pallidus, put=putamen, sept=septum.
Behavior
standard cage containing a cotton ball satured with 10% formaldehyde. The number of distinct contacts with the cotton ball was recorded for five min. Normal mice strongly avoid the odor of formaldehyde.
The behavioral observations were carried out on day 7 following surgical procedures. Approximately 24 hr before testing, each subject was placed in one half of the apparatus with the temporary partitions in place and was thus familiarized with one side of the apparatus. The floor of this half was covered with sawdust and the animal was given unlimited access to food and water. The next day, the subject was exposed to a novel object placed in the middle unit of the familiar compartment, the novel half remaining inaccessible. The object was a bakelite cylinder, 3 cm high and 3 cm in diameter. The animals were observed, in red light, for I0 min and the number of mice which showed distinct contacts with the object was recorded. Since in such a situation normal mice usually attempt to bury the object with sawdust, whether the animal was seen burying or not was also recorded. Following this test, the object was removed and 1 hr later, each subject was simultaneously given access to the familiar and novel environments by removing the partitions. This procedure did not involve removing the subject from the box. The subject was then observed for 10 rain. At the beginning of each 10-sec period indicated by a click from an electric timer, the half of the box occupied by the animal was noted. This parameter was called "novelty preference." The time sampling method was used in order to quantify, minute by minute, the preference of the novel units. This parameter represents the number of times mice were observed at the top of the 10-sec periods in the novel half. The percentage of novelty preference is defined as the number of times the animals are seen in the novel compartment divided by the total frequency (number of times in novel and familiar half) times 100. Orientation reactions to the click were never observed. Furthermore, the total number of novel and familiar units entered by the subject was also recorded and defined as locomotor activity. Finally, the number of animals eating or self-grooming was recorded.
Test of Olfaction Immediately after the test, all animals were placed in a
Histology After behavioral testing, each mouse was immediately sacrificed, the brain removed and submerged in 10% formaldehyde for 48 hr. A frozen-section technique was used in order to obtain 50 tzm coronal sections of brain tissue from the posterior to the anterior portion of the lesions in order to localize the extent of the lesions.
Statistical Analysis Novel object reactions. A Chi2-test was used to compare the number of mice in each group that showed distinct contacts with the novel object. The same test was used for the burying responses. Novelty preference. A sign test was applied to determine whether there was a preference for the novel compartment. Each animal was scored as plus or minus if it favored the novel compartment or the familiar one, respectively [11]. This test allowed us to determine at which time point each group significantly preferred the novel compartment. Finally, in order to determine the effect of the lesion on the novelty preference over the ten minute test, a two-tailed Mann-Whitney U test was used. Locomotor activity. The significance of differences of locomotor activity between lesioned mice and controls was determined by an analysis of variance. Self grooming or eating. A ChiZ-test was used to compare the number of mice that showed self-grooming or eating. RESULTS
Behavior Responses to an novel object. Twelve of the 20 lesioned mice and 1 of the 20 controls contacted the novel object, Chi 2= 13.78, p<0.001, whereas 9 lesioned mice and 17 controls buried it, Chi2=7.49, p<0.01. The caudate-putamen le-
LESIONS OF T H E C A U D A T E - P U T A M E N R E D U C E D NEOPHOBIA sion significantly increased the number of mice which showed distinct contacts with the novel object and decreased the number of mice showing burying responses. R e s p o n s e s to familiar and novel environments. The percentages of novel compartment preference in the lesioned and control mice are presented in Fig. 1. A sign-test revealed that control mice showed a significant (p<0.001) preference for novelty from the third minute on, while lesioned mice significantly (/9<0.001) preferred the novel compartments from the second minute on. However, no significant differences were found between the groups for the novelty preference over the 10 minute test. The total locomotor activity mean scores (_+SEM) of lesioned mice (112.5-+6.9) and controls (114.05-+7.18) showed no significant differences between the groups for that measure (test of analysis of variance). Finally seven of 20 lesioned mice stopped exploration and locomotor activity in order to self-groom or eat while the controls never did. Chi2=8.48, p<0.01. Histology
Histological examination of brain sections revealed little variation in the extent of the lesions. Figure 2 shows the median average of the damage. In one mouse, a minor injury to the antero-dorso-lateral part of the caudate-putamen and to the corpus callosum was observed. Test o f Olfaction
Both control and lesioned mice showed a complete avoidance to the formaldehyde-saturated cotton ball. DISCUSSION Mice were exposed to a novel object introduced into a familiar environment and were exposed to a novel environment. When exposed to a novel object, control mice showed avoidance and burying responses which can be considered as species-typical defensive behavior in mice. In contrast, the caudate-putamen-lesioned mice contacted the novel object more frequently and showed less burying responses than controls. Furthermore, when given the opportunity to move around freely in simultaneously presented novel and familiar
27
environments, control mice showed a significant preference for the novel compartment from the third minute on, while lesioned mice preferred novelty from the second minute on. Thus it would appear that the lesion had no significant effect on novelty preference except for a small effect on latency. Taken together, these data demonstrate that lesions of the caudate-putamen in mice result in a significant decrease only in neophobic components of neotic behavior. Previous findings indicated that olfaction is the primary cue for detecting even nonsocial novelty in mice [14]. The results from the present test of olfaction strongly suggest that primary sensory deficits are not involved in the present findings, since lesioned mice, like controls, showed a complete avoidance of the formaldehyde-saturated cotton ball. Furthermore, lesioned mice appeared to accurately recognize the significance of novelty, since they showed, like the controls, a significant preference for the novel environment. Nor does it seem that one can explain the decremental effects of caudate-putamen lesions on neophobia by an indirect action on locomotion, since lesioned mice and controls showed the same levels of locomotion. The present findings provide an interesting parallel between the effects arising from lesions of the caudateputamen and the well-known "amygdala-lesion syndrome." Lesions of the amygdala [15] induce the same deficit in neophobic responses in mice as damage to caudate-putamen. Moreover, the present data are consistent with the finding that striatal lesions in wild rats strongly reduce their defensive responses [3]. The striatal complex receives multiple afferent projection systems [6]. It has been suggested that the caudate-putamen could be involved in a neural mechanism which links exteroceptive sensory stimulation with the activation of normal responses, thus arousing animals to engage in adaptive behavior [2,9]. The appearance of responses released by internal stimuli, such as eating and selfgrooming that we observed in several lesioned mice strengthens this hypothesis. Indeed, these behaviors are commonly observed when animals have become habituated to novel areas or following bulbectomy and olfactory mucosa lesions [14]. This hypothesis is consistent with the recent view that animals with striatal damage "appear to be deficient in their ability to interface sensory input onto response systems" [2].
REFERENCES
1. Barnett, S. A. and P. E. Cowan. Activity, exploration, curiosity and fear: an ethological study, lnterdisciplin Sci Rev 1: 43-62, 1976. 2. Beninger, R. J. The role of dopamine in locomotor activity and learning. Brain Res Rev 6: 173-196, 1983. 3. Blanchard, D. C., R. J. Blanchard, E. M. C. Lee and G. Williams. Taming in the wild Norway Rat following lesions in the basal ganglia. Physiol Behav 27: 995-1000, 1981. 4. Corey, D. T. The determinants of exploration and neophobia. Neurosci Biobehav Rev 78: 16%177, 1981. 5. Davis, S. F., S. A. Moore, C. N. Cowen and D. K. Thurston. Defensive burying in the Mongolian gerbil (Meriones unguiculatus) as a function of size and shape of the test chamber. Anim Learn Behav 10: 516-520, 1982. 6. Feger, J. Les ganglions de la base: aspects anatomiques et 61ectrophysiologlques. J Physiol (Paris) 77: 7-44, 1979. 7. Huges, R. N. Behaviour of male and female rats with free choice of two environments differing in novelty. Anita Behav 16: 92-96, 1968.
8. Joyce, J. N., R. E. Davis and C. V. van Hartesveldt. Behavioral effects of unilateral dopamine injections into dorsal or ventral striatum. Eur J Pharmacol 72: 1-10, 1981. 9. Keller, R. W., E. M. Stricker and M. J. Zigmond. Environmental stimuli but not homeostatic challenges produce apparent increases in dopaminergic activity in the striatum: An analysis by in vivo voltammetry. Brain Res 279: 15%170, 1983. 10. Kelley, A. E., V. B. Domesick and W. J. H. Nauta. The amygdalostriatai projections in the rat: an anatomical study by anterograde and retrograde tracing methods. Neuroscience 7: 615-630, 1982. I1. Lehmann, E. L. Testing Statistical Hypotheses. New York: John Wiley and Sons, Inc, 1959, pp. 147-150. 12. Ljungberg, T. and U. Ungerstedt. Sensory inattention produced by 6-hydroxydopamine-induced degeneration of ascending dopamine neurons in the brain. Exp Neurol 53: 585-600, 1976. 13. Misslin, R. and P. Ropartz. Responses in mice to a novel object. Behaviour 78: 169-177, 1981.
28 14. Misslin, R. and P. Ropartz. Olfactory regulation of responsiveness to novelty in mice. Behav Neural Biol 33: 230-236, 1981. 15. Misslin, R. and P. Ropartz. Effects of lateral amygdala lesions on the responses to novelty in mice. Behav Process 6: 329-336, 1981. 16. Pinel, J. P. J. and D. Treit. Burying as a defensive response in rats. J Comp Physiol Psychol 92: 708-712, 1978. 17. Poling, A., J. Cleary and M. Monaghan. Burying by rats in response to aversive and nonaversive stimuli. J Exp Anal Behav 35: 31-44, 198l.
CIGRANG, VOGEL AND MISSLIN
18. Simon, H. Neurons dopaminergiques A 10 et syst6me frontal. J Physiol (Paris) 77: 81-95, 1979. 19. Treit, D., L. J. Terlecki and J. P. J. Pinel. Conditioned defensive burying: organismic variables. Bull Psychon Soc 16: 451454, 1980. 20. Wilkie, D. M., A. J. MacLennan and J. P. J. Pinel. Rat defensive behavior: burying noxious food. J Exp Anal Behav 31: 299-306, 1979.
0031-9384/86$3.00 + .00
Reduction of Neophobia in Mice Following Lesions of the Caudate-Putamen MARC CIGRANG, ELISE VOGEL AND RENE MISSLIN
Laboratoire de Psychophysiologie, 7 rue de l' Universitd F-67000 Strasbourg R e c e i v e d 12 O c t o b e r 1984 CIGRANG, M., E. VOGEL AND R. MISSLIN. Reduction of neophobia in mice following lesions of the caudateputamen. PHYSIOL BEHAV 36(1) 25-28, 1986. --Electrolytic lesions of the caudate-putamen result in a significant decrease in neophobic responses in mice towards a novel object introduced into their familiar environment; however, preference for a novel environment was not altered by the lesion. These data provide a parallel between the effects of lesions of the caudate-putamen and the well-known "amygdala-lesion-syndrome." It is suggested that the striatal complex, which receives massive afferent projection systems, plays a crucial role in sensory-motor integration processes which allow the animals to adapt their responses towards biological significant stimuli in order to cope with their environment. Putamen
Neophobia
Mice
Striatal complex
METHOD
THE striatal complex (caudate-putamen, nucleus accumbens and olfactory tubercle) is traditionally considered to be primarily motoric in function (tonic and postural regulation, initiation and smooth execution of movement). However, the anatomy of the afferent and efferent striatal projections [6,10] and recent behavioral data [8, 9, 12, 18] suggest that the striatum might be able to affect the initiation of goal directed behaviors such as responses to novelty in the environment. The term " n e o t i c " behavior has been used to describe the entire range of responses to novel stimuli including exploration, neophobia, aggression and orientation [4]. For example, a novel object introduced in a familiar environment induces avoidance and burying responses (neophobia) in rats [1] and in mice [13]. Other authors demonstrated that rats [16, 17, 20], mice [19] and Mongolian gerbils [5] shocked once by a prod buried the shock prod with bedding material. When given the opportunity to freely move around in simultaneously presented novel and familiar environments for 10 min, rats or mice spend a greater amount of time in the novel compartment (novelty preference) [7,15]. However, in this latter situation, mice first display avoidance reactions and neophobia towards a novel environment before showing a significant preference for it. Bilateral electrolytic lesions of lateral and basolateral amygdaloid nuclei in mice produce a lack of defensive responses towards novel stimuli, but do not affect their neotic preference [ 15]. Blanchard, Blanchard, Lee and Williams [3] reported that lesions in various portions of the striatum of wild rats sharply reduced the defensiveness of these animals to nonpainful stimuli. It is hypothesized that the striatal complex and its connections are important in sensori-motor integration, playing the role of an interface between the limbic system (mediating affect) and motor outputs. The present investigation attempts to study the behavioral effects of electrolytic lesions in the caudate-putamen on several neotic responses in mice.
Animals Forty adult male Swiss albino mice from our laboratory, 8 weeks of age at the time of testing, were used. Prior to experimental training, they were housed five in a standard cage containing a constant supply of food pellets and water, and kept on a 12/12 light/dark cycle with lights on at 1 a.m. They were randomly divided into two groups of 20 each. One group received bilateral electrolytic lesions of the caudateputamen, while the other served as sham-operated controls.
Surgery All subjects were operated under clean but not aseptic conditions, using sodium pentobarbital anesthesia (50 mg/kg). With the skull horizontal between bregma and lambda and using lambda as a landmark, electrodes were stereotaxically lowered to the caudate-putamen and the lesions were made electrolyticaily with an anodal current of 2 mA for a 15 sec duration. Two discrete bilateral lesions were placed in the putamen at +4.5 mm anterior to the lambda, +2 mm lateral from the midline and - 4 . 5 mm below the surface of the skull. The sham-operated subjects received the same treatment, except that the current was not delivered. After surgery, mice were immediately returned to their cage.
Apparatus The apparatus consisted of a polyvinyl chloride box (30 × 20× 20 cm), subdivided into six equal square exploratory units, all communicating by small doors, and covered with Plexiglas. It could be divided into half lengthwise by three movable doors so that the middle openings could be opened or closed. The apparatus was kept on a stand in the room which housed the mice. During observations, the experimenter, who was ignorant of the animal's treatment, always stood next to the box at the same place.
25
26
CIGRANG, VOGEL AND MISSLIN
I00
tu w it_
Ii.
50
lml
Lesioned
(
/
0 Z
/
•
/
s
!o
~
o°, ~ ,
,i
L
"~,,/'
Minutes
FIG. 1. Mean percentages of the novelty preference in caudateputamen lesioned mice (L) and sham-lesioned controls (C). Arrows show the moment after which mice displayed a significant preference for the novel compartment (sign test).
FIG. 2. The locus and extent of the damage in the caudate-putamen. cc=Corpus callosum, ca=commissura anterior, cd=nucleus caudatus, gp=globus pallidus, put=putamen, sept=septum.
Behavior
standard cage containing a cotton ball satured with 10% formaldehyde. The number of distinct contacts with the cotton ball was recorded for five min. Normal mice strongly avoid the odor of formaldehyde.
The behavioral observations were carried out on day 7 following surgical procedures. Approximately 24 hr before testing, each subject was placed in one half of the apparatus with the temporary partitions in place and was thus familiarized with one side of the apparatus. The floor of this half was covered with sawdust and the animal was given unlimited access to food and water. The next day, the subject was exposed to a novel object placed in the middle unit of the familiar compartment, the novel half remaining inaccessible. The object was a bakelite cylinder, 3 cm high and 3 cm in diameter. The animals were observed, in red light, for I0 min and the number of mice which showed distinct contacts with the object was recorded. Since in such a situation normal mice usually attempt to bury the object with sawdust, whether the animal was seen burying or not was also recorded. Following this test, the object was removed and 1 hr later, each subject was simultaneously given access to the familiar and novel environments by removing the partitions. This procedure did not involve removing the subject from the box. The subject was then observed for 10 rain. At the beginning of each 10-sec period indicated by a click from an electric timer, the half of the box occupied by the animal was noted. This parameter was called "novelty preference." The time sampling method was used in order to quantify, minute by minute, the preference of the novel units. This parameter represents the number of times mice were observed at the top of the 10-sec periods in the novel half. The percentage of novelty preference is defined as the number of times the animals are seen in the novel compartment divided by the total frequency (number of times in novel and familiar half) times 100. Orientation reactions to the click were never observed. Furthermore, the total number of novel and familiar units entered by the subject was also recorded and defined as locomotor activity. Finally, the number of animals eating or self-grooming was recorded.
Test of Olfaction Immediately after the test, all animals were placed in a
Histology After behavioral testing, each mouse was immediately sacrificed, the brain removed and submerged in 10% formaldehyde for 48 hr. A frozen-section technique was used in order to obtain 50 tzm coronal sections of brain tissue from the posterior to the anterior portion of the lesions in order to localize the extent of the lesions.
Statistical Analysis Novel object reactions. A Chi2-test was used to compare the number of mice in each group that showed distinct contacts with the novel object. The same test was used for the burying responses. Novelty preference. A sign test was applied to determine whether there was a preference for the novel compartment. Each animal was scored as plus or minus if it favored the novel compartment or the familiar one, respectively [11]. This test allowed us to determine at which time point each group significantly preferred the novel compartment. Finally, in order to determine the effect of the lesion on the novelty preference over the ten minute test, a two-tailed Mann-Whitney U test was used. Locomotor activity. The significance of differences of locomotor activity between lesioned mice and controls was determined by an analysis of variance. Self grooming or eating. A ChiZ-test was used to compare the number of mice that showed self-grooming or eating. RESULTS
Behavior Responses to an novel object. Twelve of the 20 lesioned mice and 1 of the 20 controls contacted the novel object, Chi 2= 13.78, p<0.001, whereas 9 lesioned mice and 17 controls buried it, Chi2=7.49, p<0.01. The caudate-putamen le-
LESIONS OF T H E C A U D A T E - P U T A M E N R E D U C E D NEOPHOBIA sion significantly increased the number of mice which showed distinct contacts with the novel object and decreased the number of mice showing burying responses. R e s p o n s e s to familiar and novel environments. The percentages of novel compartment preference in the lesioned and control mice are presented in Fig. 1. A sign-test revealed that control mice showed a significant (p<0.001) preference for novelty from the third minute on, while lesioned mice significantly (/9<0.001) preferred the novel compartments from the second minute on. However, no significant differences were found between the groups for the novelty preference over the 10 minute test. The total locomotor activity mean scores (_+SEM) of lesioned mice (112.5-+6.9) and controls (114.05-+7.18) showed no significant differences between the groups for that measure (test of analysis of variance). Finally seven of 20 lesioned mice stopped exploration and locomotor activity in order to self-groom or eat while the controls never did. Chi2=8.48, p<0.01. Histology
Histological examination of brain sections revealed little variation in the extent of the lesions. Figure 2 shows the median average of the damage. In one mouse, a minor injury to the antero-dorso-lateral part of the caudate-putamen and to the corpus callosum was observed. Test o f Olfaction
Both control and lesioned mice showed a complete avoidance to the formaldehyde-saturated cotton ball. DISCUSSION Mice were exposed to a novel object introduced into a familiar environment and were exposed to a novel environment. When exposed to a novel object, control mice showed avoidance and burying responses which can be considered as species-typical defensive behavior in mice. In contrast, the caudate-putamen-lesioned mice contacted the novel object more frequently and showed less burying responses than controls. Furthermore, when given the opportunity to move around freely in simultaneously presented novel and familiar
27
environments, control mice showed a significant preference for the novel compartment from the third minute on, while lesioned mice preferred novelty from the second minute on. Thus it would appear that the lesion had no significant effect on novelty preference except for a small effect on latency. Taken together, these data demonstrate that lesions of the caudate-putamen in mice result in a significant decrease only in neophobic components of neotic behavior. Previous findings indicated that olfaction is the primary cue for detecting even nonsocial novelty in mice [14]. The results from the present test of olfaction strongly suggest that primary sensory deficits are not involved in the present findings, since lesioned mice, like controls, showed a complete avoidance of the formaldehyde-saturated cotton ball. Furthermore, lesioned mice appeared to accurately recognize the significance of novelty, since they showed, like the controls, a significant preference for the novel environment. Nor does it seem that one can explain the decremental effects of caudate-putamen lesions on neophobia by an indirect action on locomotion, since lesioned mice and controls showed the same levels of locomotion. The present findings provide an interesting parallel between the effects arising from lesions of the caudateputamen and the well-known "amygdala-lesion syndrome." Lesions of the amygdala [15] induce the same deficit in neophobic responses in mice as damage to caudate-putamen. Moreover, the present data are consistent with the finding that striatal lesions in wild rats strongly reduce their defensive responses [3]. The striatal complex receives multiple afferent projection systems [6]. It has been suggested that the caudate-putamen could be involved in a neural mechanism which links exteroceptive sensory stimulation with the activation of normal responses, thus arousing animals to engage in adaptive behavior [2,9]. The appearance of responses released by internal stimuli, such as eating and selfgrooming that we observed in several lesioned mice strengthens this hypothesis. Indeed, these behaviors are commonly observed when animals have become habituated to novel areas or following bulbectomy and olfactory mucosa lesions [14]. This hypothesis is consistent with the recent view that animals with striatal damage "appear to be deficient in their ability to interface sensory input onto response systems" [2].
REFERENCES
1. Barnett, S. A. and P. E. Cowan. Activity, exploration, curiosity and fear: an ethological study, lnterdisciplin Sci Rev 1: 43-62, 1976. 2. Beninger, R. J. The role of dopamine in locomotor activity and learning. Brain Res Rev 6: 173-196, 1983. 3. Blanchard, D. C., R. J. Blanchard, E. M. C. Lee and G. Williams. Taming in the wild Norway Rat following lesions in the basal ganglia. Physiol Behav 27: 995-1000, 1981. 4. Corey, D. T. The determinants of exploration and neophobia. Neurosci Biobehav Rev 78: 16%177, 1981. 5. Davis, S. F., S. A. Moore, C. N. Cowen and D. K. Thurston. Defensive burying in the Mongolian gerbil (Meriones unguiculatus) as a function of size and shape of the test chamber. Anim Learn Behav 10: 516-520, 1982. 6. Feger, J. Les ganglions de la base: aspects anatomiques et 61ectrophysiologlques. J Physiol (Paris) 77: 7-44, 1979. 7. Huges, R. N. Behaviour of male and female rats with free choice of two environments differing in novelty. Anita Behav 16: 92-96, 1968.
8. Joyce, J. N., R. E. Davis and C. V. van Hartesveldt. Behavioral effects of unilateral dopamine injections into dorsal or ventral striatum. Eur J Pharmacol 72: 1-10, 1981. 9. Keller, R. W., E. M. Stricker and M. J. Zigmond. Environmental stimuli but not homeostatic challenges produce apparent increases in dopaminergic activity in the striatum: An analysis by in vivo voltammetry. Brain Res 279: 15%170, 1983. 10. Kelley, A. E., V. B. Domesick and W. J. H. Nauta. The amygdalostriatai projections in the rat: an anatomical study by anterograde and retrograde tracing methods. Neuroscience 7: 615-630, 1982. I1. Lehmann, E. L. Testing Statistical Hypotheses. New York: John Wiley and Sons, Inc, 1959, pp. 147-150. 12. Ljungberg, T. and U. Ungerstedt. Sensory inattention produced by 6-hydroxydopamine-induced degeneration of ascending dopamine neurons in the brain. Exp Neurol 53: 585-600, 1976. 13. Misslin, R. and P. Ropartz. Responses in mice to a novel object. Behaviour 78: 169-177, 1981.
28 14. Misslin, R. and P. Ropartz. Olfactory regulation of responsiveness to novelty in mice. Behav Neural Biol 33: 230-236, 1981. 15. Misslin, R. and P. Ropartz. Effects of lateral amygdala lesions on the responses to novelty in mice. Behav Process 6: 329-336, 1981. 16. Pinel, J. P. J. and D. Treit. Burying as a defensive response in rats. J Comp Physiol Psychol 92: 708-712, 1978. 17. Poling, A., J. Cleary and M. Monaghan. Burying by rats in response to aversive and nonaversive stimuli. J Exp Anal Behav 35: 31-44, 198l.
CIGRANG, VOGEL AND MISSLIN
18. Simon, H. Neurons dopaminergiques A 10 et syst6me frontal. J Physiol (Paris) 77: 81-95, 1979. 19. Treit, D., L. J. Terlecki and J. P. J. Pinel. Conditioned defensive burying: organismic variables. Bull Psychon Soc 16: 451454, 1980. 20. Wilkie, D. M., A. J. MacLennan and J. P. J. Pinel. Rat defensive behavior: burying noxious food. J Exp Anal Behav 31: 299-306, 1979.