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Greater Behavioral Effects of Stress in Immature as Compared to Mature Male Mice
Physiology & Behavior, Vol. 63, No. 1, pp. 143–145, 1998 © 1998 Elsevier Science Inc. All rights reserved. Printed in the U.S.A. 0031-9384/98 $19.00 1 .00
PII S0031-9384(97)00366-1
BRIEF COMMUNICATION
Greater Behavioral Effects of Stress in Immature as Compared to Mature Male Mice ERIC A. STONE1* AND DAVID QUARTERMAIN† Departments of *Psychiatry and †Neurology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA Received 28 February 1997; Accepted 1 July 1997 STONE, E. A. AND D. QUARTERMAIN. Greater behavioral effects of stress in immature as compared to mature male mice. PHYSIOL BEHAV 63(1) 143–145, 1998.—The effect of sexual maturity on behavioral effects of stress was examined in male mice. Immature (4-week-old) or mature (8-week-old) animals were subjected to either social stress (exposure to an isolated adult male) or restraint stress for 5 days and examined for body weight, food intake, or plus-maze behavior. Social stress reduced food intake, body weight, and open-arm entries in 4-week-old but not 8-week-old mice. Restraint reduced body weight in 4-week-old but not 8-week-old mice. It is concluded that immature male mice show greater behavioral disturbances after stress than their mature counterparts. The findings are in agreement with much anecdotal evidence that children are more vulnerable to stress than adults. © 1998 Elsevier Science Inc. Stress
Maturity
Body weight
Food intake
Plus maze
ments so the experiments started when the animals were 4 and 8.5 (hereafter referred to as 8) weeks of age. Food was present ad lib. and a 12 h:12 h light– dark cycle was imposed (lights on 0700 hours). The animals were subjected to one of two forms of stress, social or restraint stress. For social stress the mice were placed for 5 min/day in the cage of an isolated adult male. Observations were made during this period as to whether the resident mouse attacked the intruder or not. For restraint the animals were placed in a tapered cylindrical tube (3 cm at its widest aspect) with an adjustable plunger for a 1-h period. Both stressors were administered at 1200 hours on 5 consecutive days. Body weights were obtained prior to and on the day following the last stress. Food intake was determined daily from preweighed pellets placed on the floor of the cage. Plus-maze behavior was recorded for 5 min on the day following the last stress as described previously (24). During the social stress no instances of attack by the resident mouse on the 4-week-old animals was observed whereas all the 8-week-old intruders were attacked during each exposure. The effects of social stress on food intake in the 4- and 8-week-old mice are shown in Fig. 1A,B. There was a tendency of intake to increase in all groups over the 5-day period, which we have observed previously in single housed male mice. The stress resulted in a significant decrease in food intake of the 4-week-old mice (F(1, 12) 5 11.3, p , 0.01) but not of the 8-week-old animals (F(1, 12) 5 2.51, NS). Similarly, the body weights of the 4-week-old animals were significantly depressed by the stress but
STRESS has been shown to produce a wide range of behavioral and physiological changes. These include anxiety (13,15,22,28), hypoactivity (5,26,27), anorexia (2,11,23), weight loss (6), reduced aggression (17,18,29), and hyposexuality (21) among others. Much anecdotal and clinical evidence suggests that young animals and humans are more sensitive to stress than mature ones (19,20,25). Thus lasting behavioral changes can be produced by stressors in young organisms (4,12,16). Most experimental work in this area however has utilized infant animals whose behavioral repertoires are limited. However, there have been isolated reports using immature behaviorally competent animals that effects of stress are greater in immature as compared to mature animals. Thus immature male fish have been found to have larger corticosterone responses to stress than mature male fish (14) and adolescent golden hamsters have been shown to have increased vulnerability to social stress (7). The relationship between maturity and vulnerability to stress is still however largely unexplored. The present experiments were therefore undertaken to examine this factor by measuring the behavioral effects of stress in mature and immature mice. Male Swiss Webster (Taconic Farms) mice 3.5 or 8 weeks old weaned at 21 days were used as subjects. Based on breeding potency, puberty occurs in males of this strain from this supplier at 5-6 weeks of age (J. Geistfeld, Taconic Farms, personal communication). The animals were housed singly in standard mouse cages with nesting material for 3 days prior to the start of the experi1
To whom requests for reprints should be addressed. E-mail: [email protected]
143
144
STONE AND QUARTERMAIN TABLE 1 EFFECT OF SOCIAL OR RESTRAINT STRESS ON THE BODY WEIGHTS OF 4- AND 8-WEEK-OLD MALE MICE 4-Week-Old
8-Week-Old
Social Stress Control Stress
22.5 6 0.5 19.0 6 0.5**
Control Stress
23.2 6 0.4 21.3 6 0.4*
36.8 6 1.2 35.5 6 1.0 Restraint Stress 36.6 6 0.6 36.0 6 0.7
Values are means and SEMs of 7 animals. **p , 0.001, *p , 0.05 versus control group.
FIG. 1. Effect of social stress on food intake in 4-week-old (A) and 8-week-old (B) male mice. Circles represent controls, squares, stressed animals. Values represent means and SEMs of seven animals.
defend themselves as we observed no attacking by the resident adult males on the 4-week-old intruding males although considerable attacking of the 8-week-old intruding males occurred. Although this behavioral difference during the stress may have contributed to the differential aftereffects, this is unlikely because the presence of attacks would be expected to increase rather than decrease the magnitude of the stress effect. The increased stress effects of the younger males were also unlikely to be related to their smaller size since restraint stress was accomplished with an adjustable restrainer which restricted the activity of immature and mature animals similarly independent of size. The biological basis for the increased stress effects in immature animals is not known. One factor however may be the lack of testosterone secretion. Testosterone has been found to reduce behavioral and corticosterone responses to stress in rats (10), heifers (3), and rainbow trout (14) and female rats of various strains show higher corticosterone responses to stress than males (1). Although plasma testosterone was not measured in the present study, 4-week-old rodents are known to have testicular weight/ body weight ratios one-half that of 8 week olds and not to achieve the adult ratio until 8 weeks of age (8). Early abuse is a major etiological factor in psychiatric illness (9,19,20,25). The increased behavioral effects of stress in immature male mice might prove useful in investigating the susceptibility of young organisms to stress. ACKNOWLEDGEMENT
those of the 8-week-old mice were not (Table 1). The performance of the animals in the plus maze is shown in Table 2. The stressed 4-week-old animals showed a significant decrease in the number of open arms entered but the stressed 8 week olds did not. The number of closed-arm entries and the ratio of open to closed entries did not differ between the groups. Restraint had no effect on the food intake of either group (data not shown) but significantly depressed the body weights of the 4-week-old but not 8-week-old mice (Table 2). The effect of restraint was not tested on plus-maze behavior. The present results suggest that sexual maturity may be a factor in determining vulnerability to stress effects in male mice. Mature males were less disturbed by social stress in terms of decreases in food intake, body weight, and plus-maze behavior than their immature counterparts. This was unlikely to be peculiar to social stress since a similar weight difference was obtained with restraint stress. The increased stress effects in the younger males to social stress were unlikely to be due to a lower ability to physically
This work was supported in part by Grant MH45265 and a Stanley Foundation award.
TABLE 2 EFFECT OF SOCIAL STRESS ON PLUS-MAZE BEHAVIOR IN 4- OR 8-WEEK-OLD MALE MICE Open Arms
Control Stress
5.4 6 1.4 2.0 6 0.6*
Control Stress
4.2 6 1.4 3.6 6 1.4
Closed Arms
4 Week Olds 6.1 6 1.4 4.1 6 1.0 8 Week Olds 6.0 6 1.7 8.2 6 2.1
Ratio O/C
0.41 6 0.06 0.27 6 0.07 0.38 6 0.11 0.24 6 0.08
Values are means and SEMs of 7-9 animals. *p , 0.05 versus control group.
BEHAVIORAL EFFECTS OF STRESS IN MICE
145 REFERENCES
1. Armario, A.; Gavalda, A.; Marti, J. Comparison of the behavioral and endocrine response to forced swimming stress in five inbred strains of rats. Psychoneuroendocrinology 20:879 – 890; 1995. 2. Blanchard, R. J.; Blanchard, D. C.; Rodgers, J.; Weiss, S. M. The characterization and modelling of antipredator defensive behavior. Neurosci. Biobehav. Rev. 14:463– 472; 1990. 3. Boissy, A.; Bouissou, M. F. Effects of androgen treatment on behavioral and physiological responses of heifers to fear-eliciting situations. Horm. Behav. 28:66 – 82; 1994. 4. Costela, C.; Tejedor-Real, F.; Mico, J. A.; Gibert-Rahola, J. Effect of neonatal handling on learned helplessness model of depression. Physiol. Behav. 57:407– 410; 1995. 5. Desan, P. H.; Silbert, L. H.; Maier, S. F. Long-term effects of inescapable stress on daily running activity and antagonism by desipramine. Pharmacol. Biochem. Behav. 30:21–29; 1988. 6. Dess, N. K.; Minor, T. R.; Brewer, J. Suppression of feeding and body weight by inescapable shock: Modulation by quinine adulteration, stress reinstatement, and controllability. Physiol. Behav. 45:975–983; 1989. 7. Ferris, C. E.; Melloni, R. H.; Abbott, M. A.; Delville, Y. Behavioral and neurobiological consequences of adolescent abuse in golden hamsters. Abstr. Soc. Neurosci. 21:1695; 1995. 8. Flickinger, C. J.; Herr, J. C.; Baran, M. L.; Howards, S. S. Testicular development and the formation of spermatic granulomas of the epididymis after obstruction of the vas deferens in immature rats. J. Urol. 154:1539 –1544; 1995. 9. Gross, A. B.; Keller, H. R. Long-term consequences of childhood physical and psychological maltreatment. Aggress. Behav. 18:171– 185; 1992. 10. Handa, R. F.; Nunley, K. M.; Lorens, S. A.; Louie, J. P.; McGivern, R. F.; Bollnow, M. R. Androgen regulation of adrenocorticotropin and corticosterone secretion in the male rat following novelty and foot shock stressors. Physiol. Behav. 55:117–124; 1994. 11. Krahn, D. D.; Gosnell, B. A.; Majchrzak, M. J. The anorectic effects of CRH and restraint stress decrease with repeated exposures. Biol. Psychiat. 27:1094 –1102; 1990. 12. Martin, L. J.; Spicer, D. M.; Lewis, M. H.; Gluck, J. P.; Cork, L. C. Social deprivation of infant rhesus monkeys alters the chemoarchitecture of the brain: I. Subcortical regions. J. Neurosci. 11:3344 –3358; 1991. 13. Ottenweller, J. E.; Servatius, R. J.; Tapp, W. N.; Drastal, S. D.; Bergen, M. T.; Natelson, B. H. A chronic stress state in rats: Effects of repeated stress on basal corticosterone and behavior. Physiol. Behav. 51:689 – 698; 1992. 14. Pottinger, T. G.; Balm, P. H. B.; Pickering, A. D. Sexual maturity modifies the responsiveness of the pituitary-interrenal axis to stress in male rainbow trout. Gen. Comp. Endocrinol. 98:311–320; 1995.
15. Rodgers, R. J.; Cole, J. C. Anxiety enhancement in the murine elevated plus maze by immediate prior exposure to social stressors. Physiol. Behav. 53:383–388; 1993. 16. Rosenblum, L. A.; Coplan, J. D.; Friedman, S.; Bassoff, T.; Gorman, J. M.; Andrews, M. W. Adverse early experiences affect noradrenergic and serotonergic functioning in adult primates. Biol. Psychiat. 35:221– 227; 1994. 17. Roth, W. T.; Ehlers, A.; Taylor, C. B.; Margraf, J.; Agras, W. S. Skin conductance habituation in panic disorder patients. Biol. Psychiat. 27:1231–1243; 1990. 18. Scholtens, J.; Roozen, M.; Mirmiran, M.; van de Poll, N. E. Role of noradrenaline in behavioral changes after defeat in male and female rats. Behav. Brain. Res. 36:199 –202; 1990. 19. Shearer, S. L.; Peters, C. P.; Quaytman, M. S.; Ogden, R. L. Frequency and correlates of childhood sexual and physical abuse histories in adult female borderline inpatients. Am. J. Psychiat. 147:214 –216; 1990. 20. Sheldon, H. Childhood sexual abuse in adult female psychotherapy referrals. Br. J. Psychiat. 152:107–111; 1988. 21. Sirvio, J.; Riekkinen, P. J.; Valjakka, A.; Jolkkonen, J.; Riekkinen, P. J. The effects of noradrenergic neurotoxin, DSP-4, on the performance of young and aged rats in spatial navigation task. Brain Res. 563:297–302; 1991. 22. Steenbergen, H. L.; Farabollini, F.; Heinsbroek, R. P. W.; van de Poll, N. E. Sex-dependent effects of aversive stimulation on holeboard and elevated plus-maze behavior. Behav. Brain Res. 43:159 –165; 1991. 23. Stone, E. A.; Platt, J. E. Brain adrenergic receptors and resistance to stress. Brain Res. 237:405– 414; 1982. 24. Stone, E. A.; Zhang, Y.; Quartermain, D. The effect of stress on spontaneous nest leaving behavior in the mouse: An improved model of stress-induced behavioral pathology. Stress 3:145–154; 1997. 25. Swett, C., Jr.; Surrey, J.; Cohen, C. Sexual and physical abuse histories and psychiatric symptoms among male psychiatric outpatients. Am. J. Psychiat. 147:632– 636; 1990. 26. Weiss, J. M.; Goodman, P. A.; Losito, B. G.; Corrigan, S.; Charry, J. M.; Bailey, W. H. Behavioral depression produced by an uncontrollable stressor: Relationship to norepinephrine, dopamine and serotonin levels in various regions of rat brain. Brain Res. Rev. 3:167–205; 1981. 27. Woodmansee, W. W.; Silbert, L. H.; Maier, S. F. Factors that modulate inescapable shock-induced reductions in daily activity in the rat. Pharmacol. Biochem. Behav. 45:553–559; 1993. 28. Yang, X.-M.; Gorman, A. L.; Dunn, A. J. The involvement of central noradrenergic systems and corticotropin-releasing factor in defensivewithdrawal behavior in rats. J. Pharmacol. Exp. Therap. 255:1064 – 1070; 1990. 29. Zebrowska-Lupina, I.; Ossowska, G.; Klenk-Majewska, B. Chronic stress reduces fighting behavior of rats: The effect of antidepressants. Pharmacol. Biochem. Behav. 39:293–296; 1991.
PII S0031-9384(97)00366-1
BRIEF COMMUNICATION
Greater Behavioral Effects of Stress in Immature as Compared to Mature Male Mice ERIC A. STONE1* AND DAVID QUARTERMAIN† Departments of *Psychiatry and †Neurology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA Received 28 February 1997; Accepted 1 July 1997 STONE, E. A. AND D. QUARTERMAIN. Greater behavioral effects of stress in immature as compared to mature male mice. PHYSIOL BEHAV 63(1) 143–145, 1998.—The effect of sexual maturity on behavioral effects of stress was examined in male mice. Immature (4-week-old) or mature (8-week-old) animals were subjected to either social stress (exposure to an isolated adult male) or restraint stress for 5 days and examined for body weight, food intake, or plus-maze behavior. Social stress reduced food intake, body weight, and open-arm entries in 4-week-old but not 8-week-old mice. Restraint reduced body weight in 4-week-old but not 8-week-old mice. It is concluded that immature male mice show greater behavioral disturbances after stress than their mature counterparts. The findings are in agreement with much anecdotal evidence that children are more vulnerable to stress than adults. © 1998 Elsevier Science Inc. Stress
Maturity
Body weight
Food intake
Plus maze
ments so the experiments started when the animals were 4 and 8.5 (hereafter referred to as 8) weeks of age. Food was present ad lib. and a 12 h:12 h light– dark cycle was imposed (lights on 0700 hours). The animals were subjected to one of two forms of stress, social or restraint stress. For social stress the mice were placed for 5 min/day in the cage of an isolated adult male. Observations were made during this period as to whether the resident mouse attacked the intruder or not. For restraint the animals were placed in a tapered cylindrical tube (3 cm at its widest aspect) with an adjustable plunger for a 1-h period. Both stressors were administered at 1200 hours on 5 consecutive days. Body weights were obtained prior to and on the day following the last stress. Food intake was determined daily from preweighed pellets placed on the floor of the cage. Plus-maze behavior was recorded for 5 min on the day following the last stress as described previously (24). During the social stress no instances of attack by the resident mouse on the 4-week-old animals was observed whereas all the 8-week-old intruders were attacked during each exposure. The effects of social stress on food intake in the 4- and 8-week-old mice are shown in Fig. 1A,B. There was a tendency of intake to increase in all groups over the 5-day period, which we have observed previously in single housed male mice. The stress resulted in a significant decrease in food intake of the 4-week-old mice (F(1, 12) 5 11.3, p , 0.01) but not of the 8-week-old animals (F(1, 12) 5 2.51, NS). Similarly, the body weights of the 4-week-old animals were significantly depressed by the stress but
STRESS has been shown to produce a wide range of behavioral and physiological changes. These include anxiety (13,15,22,28), hypoactivity (5,26,27), anorexia (2,11,23), weight loss (6), reduced aggression (17,18,29), and hyposexuality (21) among others. Much anecdotal and clinical evidence suggests that young animals and humans are more sensitive to stress than mature ones (19,20,25). Thus lasting behavioral changes can be produced by stressors in young organisms (4,12,16). Most experimental work in this area however has utilized infant animals whose behavioral repertoires are limited. However, there have been isolated reports using immature behaviorally competent animals that effects of stress are greater in immature as compared to mature animals. Thus immature male fish have been found to have larger corticosterone responses to stress than mature male fish (14) and adolescent golden hamsters have been shown to have increased vulnerability to social stress (7). The relationship between maturity and vulnerability to stress is still however largely unexplored. The present experiments were therefore undertaken to examine this factor by measuring the behavioral effects of stress in mature and immature mice. Male Swiss Webster (Taconic Farms) mice 3.5 or 8 weeks old weaned at 21 days were used as subjects. Based on breeding potency, puberty occurs in males of this strain from this supplier at 5-6 weeks of age (J. Geistfeld, Taconic Farms, personal communication). The animals were housed singly in standard mouse cages with nesting material for 3 days prior to the start of the experi1
To whom requests for reprints should be addressed. E-mail: [email protected]
143
144
STONE AND QUARTERMAIN TABLE 1 EFFECT OF SOCIAL OR RESTRAINT STRESS ON THE BODY WEIGHTS OF 4- AND 8-WEEK-OLD MALE MICE 4-Week-Old
8-Week-Old
Social Stress Control Stress
22.5 6 0.5 19.0 6 0.5**
Control Stress
23.2 6 0.4 21.3 6 0.4*
36.8 6 1.2 35.5 6 1.0 Restraint Stress 36.6 6 0.6 36.0 6 0.7
Values are means and SEMs of 7 animals. **p , 0.001, *p , 0.05 versus control group.
FIG. 1. Effect of social stress on food intake in 4-week-old (A) and 8-week-old (B) male mice. Circles represent controls, squares, stressed animals. Values represent means and SEMs of seven animals.
defend themselves as we observed no attacking by the resident adult males on the 4-week-old intruding males although considerable attacking of the 8-week-old intruding males occurred. Although this behavioral difference during the stress may have contributed to the differential aftereffects, this is unlikely because the presence of attacks would be expected to increase rather than decrease the magnitude of the stress effect. The increased stress effects of the younger males were also unlikely to be related to their smaller size since restraint stress was accomplished with an adjustable restrainer which restricted the activity of immature and mature animals similarly independent of size. The biological basis for the increased stress effects in immature animals is not known. One factor however may be the lack of testosterone secretion. Testosterone has been found to reduce behavioral and corticosterone responses to stress in rats (10), heifers (3), and rainbow trout (14) and female rats of various strains show higher corticosterone responses to stress than males (1). Although plasma testosterone was not measured in the present study, 4-week-old rodents are known to have testicular weight/ body weight ratios one-half that of 8 week olds and not to achieve the adult ratio until 8 weeks of age (8). Early abuse is a major etiological factor in psychiatric illness (9,19,20,25). The increased behavioral effects of stress in immature male mice might prove useful in investigating the susceptibility of young organisms to stress. ACKNOWLEDGEMENT
those of the 8-week-old mice were not (Table 1). The performance of the animals in the plus maze is shown in Table 2. The stressed 4-week-old animals showed a significant decrease in the number of open arms entered but the stressed 8 week olds did not. The number of closed-arm entries and the ratio of open to closed entries did not differ between the groups. Restraint had no effect on the food intake of either group (data not shown) but significantly depressed the body weights of the 4-week-old but not 8-week-old mice (Table 2). The effect of restraint was not tested on plus-maze behavior. The present results suggest that sexual maturity may be a factor in determining vulnerability to stress effects in male mice. Mature males were less disturbed by social stress in terms of decreases in food intake, body weight, and plus-maze behavior than their immature counterparts. This was unlikely to be peculiar to social stress since a similar weight difference was obtained with restraint stress. The increased stress effects in the younger males to social stress were unlikely to be due to a lower ability to physically
This work was supported in part by Grant MH45265 and a Stanley Foundation award.
TABLE 2 EFFECT OF SOCIAL STRESS ON PLUS-MAZE BEHAVIOR IN 4- OR 8-WEEK-OLD MALE MICE Open Arms
Control Stress
5.4 6 1.4 2.0 6 0.6*
Control Stress
4.2 6 1.4 3.6 6 1.4
Closed Arms
4 Week Olds 6.1 6 1.4 4.1 6 1.0 8 Week Olds 6.0 6 1.7 8.2 6 2.1
Ratio O/C
0.41 6 0.06 0.27 6 0.07 0.38 6 0.11 0.24 6 0.08
Values are means and SEMs of 7-9 animals. *p , 0.05 versus control group.
BEHAVIORAL EFFECTS OF STRESS IN MICE
145 REFERENCES
1. Armario, A.; Gavalda, A.; Marti, J. Comparison of the behavioral and endocrine response to forced swimming stress in five inbred strains of rats. Psychoneuroendocrinology 20:879 – 890; 1995. 2. Blanchard, R. J.; Blanchard, D. C.; Rodgers, J.; Weiss, S. M. The characterization and modelling of antipredator defensive behavior. Neurosci. Biobehav. Rev. 14:463– 472; 1990. 3. Boissy, A.; Bouissou, M. F. Effects of androgen treatment on behavioral and physiological responses of heifers to fear-eliciting situations. Horm. Behav. 28:66 – 82; 1994. 4. Costela, C.; Tejedor-Real, F.; Mico, J. A.; Gibert-Rahola, J. Effect of neonatal handling on learned helplessness model of depression. Physiol. Behav. 57:407– 410; 1995. 5. Desan, P. H.; Silbert, L. H.; Maier, S. F. Long-term effects of inescapable stress on daily running activity and antagonism by desipramine. Pharmacol. Biochem. Behav. 30:21–29; 1988. 6. Dess, N. K.; Minor, T. R.; Brewer, J. Suppression of feeding and body weight by inescapable shock: Modulation by quinine adulteration, stress reinstatement, and controllability. Physiol. Behav. 45:975–983; 1989. 7. Ferris, C. E.; Melloni, R. H.; Abbott, M. A.; Delville, Y. Behavioral and neurobiological consequences of adolescent abuse in golden hamsters. Abstr. Soc. Neurosci. 21:1695; 1995. 8. Flickinger, C. J.; Herr, J. C.; Baran, M. L.; Howards, S. S. Testicular development and the formation of spermatic granulomas of the epididymis after obstruction of the vas deferens in immature rats. J. Urol. 154:1539 –1544; 1995. 9. Gross, A. B.; Keller, H. R. Long-term consequences of childhood physical and psychological maltreatment. Aggress. Behav. 18:171– 185; 1992. 10. Handa, R. F.; Nunley, K. M.; Lorens, S. A.; Louie, J. P.; McGivern, R. F.; Bollnow, M. R. Androgen regulation of adrenocorticotropin and corticosterone secretion in the male rat following novelty and foot shock stressors. Physiol. Behav. 55:117–124; 1994. 11. Krahn, D. D.; Gosnell, B. A.; Majchrzak, M. J. The anorectic effects of CRH and restraint stress decrease with repeated exposures. Biol. Psychiat. 27:1094 –1102; 1990. 12. Martin, L. J.; Spicer, D. M.; Lewis, M. H.; Gluck, J. P.; Cork, L. C. Social deprivation of infant rhesus monkeys alters the chemoarchitecture of the brain: I. Subcortical regions. J. Neurosci. 11:3344 –3358; 1991. 13. Ottenweller, J. E.; Servatius, R. J.; Tapp, W. N.; Drastal, S. D.; Bergen, M. T.; Natelson, B. H. A chronic stress state in rats: Effects of repeated stress on basal corticosterone and behavior. Physiol. Behav. 51:689 – 698; 1992. 14. Pottinger, T. G.; Balm, P. H. B.; Pickering, A. D. Sexual maturity modifies the responsiveness of the pituitary-interrenal axis to stress in male rainbow trout. Gen. Comp. Endocrinol. 98:311–320; 1995.
15. Rodgers, R. J.; Cole, J. C. Anxiety enhancement in the murine elevated plus maze by immediate prior exposure to social stressors. Physiol. Behav. 53:383–388; 1993. 16. Rosenblum, L. A.; Coplan, J. D.; Friedman, S.; Bassoff, T.; Gorman, J. M.; Andrews, M. W. Adverse early experiences affect noradrenergic and serotonergic functioning in adult primates. Biol. Psychiat. 35:221– 227; 1994. 17. Roth, W. T.; Ehlers, A.; Taylor, C. B.; Margraf, J.; Agras, W. S. Skin conductance habituation in panic disorder patients. Biol. Psychiat. 27:1231–1243; 1990. 18. Scholtens, J.; Roozen, M.; Mirmiran, M.; van de Poll, N. E. Role of noradrenaline in behavioral changes after defeat in male and female rats. Behav. Brain. Res. 36:199 –202; 1990. 19. Shearer, S. L.; Peters, C. P.; Quaytman, M. S.; Ogden, R. L. Frequency and correlates of childhood sexual and physical abuse histories in adult female borderline inpatients. Am. J. Psychiat. 147:214 –216; 1990. 20. Sheldon, H. Childhood sexual abuse in adult female psychotherapy referrals. Br. J. Psychiat. 152:107–111; 1988. 21. Sirvio, J.; Riekkinen, P. J.; Valjakka, A.; Jolkkonen, J.; Riekkinen, P. J. The effects of noradrenergic neurotoxin, DSP-4, on the performance of young and aged rats in spatial navigation task. Brain Res. 563:297–302; 1991. 22. Steenbergen, H. L.; Farabollini, F.; Heinsbroek, R. P. W.; van de Poll, N. E. Sex-dependent effects of aversive stimulation on holeboard and elevated plus-maze behavior. Behav. Brain Res. 43:159 –165; 1991. 23. Stone, E. A.; Platt, J. E. Brain adrenergic receptors and resistance to stress. Brain Res. 237:405– 414; 1982. 24. Stone, E. A.; Zhang, Y.; Quartermain, D. The effect of stress on spontaneous nest leaving behavior in the mouse: An improved model of stress-induced behavioral pathology. Stress 3:145–154; 1997. 25. Swett, C., Jr.; Surrey, J.; Cohen, C. Sexual and physical abuse histories and psychiatric symptoms among male psychiatric outpatients. Am. J. Psychiat. 147:632– 636; 1990. 26. Weiss, J. M.; Goodman, P. A.; Losito, B. G.; Corrigan, S.; Charry, J. M.; Bailey, W. H. Behavioral depression produced by an uncontrollable stressor: Relationship to norepinephrine, dopamine and serotonin levels in various regions of rat brain. Brain Res. Rev. 3:167–205; 1981. 27. Woodmansee, W. W.; Silbert, L. H.; Maier, S. F. Factors that modulate inescapable shock-induced reductions in daily activity in the rat. Pharmacol. Biochem. Behav. 45:553–559; 1993. 28. Yang, X.-M.; Gorman, A. L.; Dunn, A. J. The involvement of central noradrenergic systems and corticotropin-releasing factor in defensivewithdrawal behavior in rats. J. Pharmacol. Exp. Therap. 255:1064 – 1070; 1990. 29. Zebrowska-Lupina, I.; Ossowska, G.; Klenk-Majewska, B. Chronic stress reduces fighting behavior of rats: The effect of antidepressants. Pharmacol. Biochem. Behav. 39:293–296; 1991.