Suppression of pituitary-adrenal activity and shock-induced fighting in rats

The effect on shock-induced fighting behavior in adult male rats of an implant of 250 ± 25 μg crystalline hydrocortisone acetate in the median eminence of the hypothalamus was investigated. No behavioral differences were found between the eight pairs of hydrocortisone-implanted and sham-implanted animals. Measures of plasma corticosterone prior to testing and immediately following the last fighting session and adrenal and pituitary weights at autopsy showed a complete suppression of pituitary-adrenal activity in the experimental group. Mediation of agonistic behavior by ACTH and corticoids previously reported was not confirmed in this test situation.     

Pituitary-adrenocortical axis and shock-induced fighting in rats.

Two experiments were designed to investigate pituitary-adrenocortical influences on shock-induced fighting in rats. In the first experiment, the effects of adrenalectomy, hypophysectomy, hydrocortisone and ACTH (2 dose levels) on shock-induced fighting were examined. Adrenalectomy, hypophysectomy and the high dose of ACTH suppressed fighting behaviour whilst hydrocortisone and the low dose of ACTH augmented this response. The second experiment, performed to determine whether these hormonal manipulations modified shock sensitivity, revealed that none of the treatments significantly altered shock thresholds. Results are discussed in relation to known influences of pituitary-adrenal secretions on fear-motivated behaviours and limbic system activity.     

Effects of prepubertal handling on shock-induced fighting and ACTH in male and female rats.

Rats which received either handling from Days 1–14 (EH) or 22–35 (LH) of life or no handling (NH) were tested in the shock-induced fighting situation in adulthood. Ten males and 10 females from each group were either paired for fighting (F), shocked singly (S), or received no shock (N) in the test chamber for 4.5 min in 3 sessions given 48 hr apart. Immediately after the third test session, trunk blood was obtained for determination of plasma ACTH concentrations. Males and females did not differ with respect to fighting frequency in response to shock, but males displayed the fighting posture substantially more than did females. Rats handled either preweaning (EH) or postweaning (LH) fought more often at the two lower shock intensities (0.5 and 1.3 mA) than did nonhandled controls (NH). The incidence of fighting positions did not differ as a function of prior handling. In all groups but one, the pattern of ACTH response to the different test conditions coincided with previous reports: higher levels of ACTH were found in response to shock alone than in response to fighting plus shock, and the lowest levels were found in the nonshocked controls. In the exceptional group, the NH males (but not females), there was a nondiscriminatory ACTH response to the S and F test conditions. The effects of prior handling are discussed in terms of an enhanced coping ability. The results point to the importance of comparing both pre- and postweaning groups when studying the handling phenomenon.     

Effects of chronic stress on plasma corticosterone, ACTH and prolactin

Rats were placed in a stressful environment for 24 hr per day and levels of plasma hormones were measured after varying numbers of days in the environment. Rats were habituated to operant chambers placed in sound-attenuated enclosures. Food pellets were available by lever press on a FR1 schedule. After 3 days of habituation, rats in the “stressed” group were trained to pull a ceiling chain to avoid or escape shock. Following training, stress trials, consisting of a consecutive sequence of 5 sec each of a warning light, warning tone and 0.16, 0.32, 0.65, 1.3 and 2.6 mA of footshock, occurred approximately once per 5 min around-the-clock. For the first day, the sequence was terminated when the ceiling chain was pulled. On subsequent days, 90% of all shock presentations could be avoided or escaped by chain pull; the remaining 10% of trials were inescapable and the entire sequence was presented. Control rats lived in identical chambers without presentation of shock. Rats were sacrificed after 1, 2, 3, 4, 7 or 14 days in this environment and levels of plasma corticosterone, ACTH and prolactin were determined. Levels of plasma corticosterone were elevated during the first 7 days in the stressful environment, but returned to control values by day 14. Levels of plasma ACTH and prolactin were similar in stressed and control rats at all time points measured. These data suggest that stress-induced changes in glucocorticoids but not in ACTH or prolactin might mediate some of the physiological changes that occur as the result of chronic stress.     

Shock-induced fighting attenuates the effects of prior shock experience in rats

We compared the responses of animals exposed singly to inescapable shock with those of animals exposed to the same shock in pairs and thus able to fight in response to shock. During the shock sessions animals shocked in pairs showed a reduced ACTH response when compared with animals shocked individually, and the reduction in ACTH was not dependent on the amount of fighting which occurred. In addition, if animals had previous opportunities to fight, the response to shock was still attenuated even when the partner was no longer present. When subsequently tested in a novel task it was observed that fighters, like controls, showed a reduced pituitary-adrenal response to novelty when a consummatory response was available. Singly shocked animals, however, exhibited elevated levels of plasma corticosterone whether or not they could drink in the novel chamber. We hypothesized that fighting is a consummatory response, and that the reinforcement provided by performance of this consummatory response reduced the ACTH response to shock and permanently altered subsequent responsiveness.     

Effect of fornix lesions on shock-induced aggression, muricide and motor behavior in the albino rat

The role of the fornix in aggressive and motor behavior was assessed in three experiments. In Experiment 1 a substantially lower fighting frequency was observed in shock-induced aggression in the fornix lesioned group as compared to sham operated control animals. Experiment 2 attempted to relate this low fighting frequency to a lesion-induced decrease in motor responsivity and also to determine whether another form of aggressive behavior, muricide, was affected by damage to the fornix. A battery of motor tests revealed a deficiency in motor responsivity which coexisted with low shock-induced fighting frequencies in lesioned animals. However, muricidal behavior was not affected. In Experiment 3 no change in shock-induced fighting frequencies were found in animals which had previous experience with this form of aggression, despite significant changes in motor responsivity. The results were interpreted to indicate that the hippocampus affects motor behavior through the extrapyramidal motor system and plays a substantial role in shock-induced fighting behavior. It is concluded that the effects of fornix lesions on aggressive behavior and motor ability are independent phenomena.     

Effects of ether stress on prolactin and corticosterone levels in prenatally-stressed male rats as adults

The effect of a potent prenatal stressor on adult levels of prolactin and corticosterone was investigated in male rats. It was found that prenatal stress had no effect on initial levels of either of these two hormones. Ether stress levels of prolactin were significantly lower in prenatally-stressed animals compared to prenatally-nonstressed subjects, whereas corticosterone levels in response to ether stress were only marginally affected in prenatally-stressed animals reared by prepartally-stressed mothers. It is suggested that alterations in endocrine function in the adult animal may result from prenatal stress effects on the development of neural mechanisms that regulate the hormonal response to ether stress.     

Effects of electrochemical stimulation of the hypothalamus on serum prolactin and LH in rats

Summary Plasma levels of prolactin and LH were measured by radioimmunoassay following electrochemical stimulation of the medial preoptic area (MPO) or the arcuate nucleus (Arc.N.) in pentobarbital anesthetized proestrous rats. Differences in the secretion pattern of prolactin and LH were observed when stimulated by means of acutely or chronically implanted electrodes. Acute implantation and stimulation of the MPO resulted in no change in serum prolactin levels, whereas stimulation by means of chronically implanted electrodes evoked a marked increase in serum prolactin. The general observation was that electrostimulation in the acute experiments causes a less sharp but more prolonged prolactin and LH release from pituitary than stimulation through chronically implanted electrodes.Aided in part by NIH research grants CA 10771 and AM 4784.     

Temporal effects of castration on emotionality and shock-induced aggression in adult male rats.

Alterations in shock-induced aggressive behavior, general emotional reactivity and flinch thresholds in 61 and 82 day old male rats were analyzed at either 3 or 6 weeks following castration. Castrated animals were significantly less aggressive than sham-operated controls at the 6 week but not the 3 week interval. These findings could not be attributed to changes in flinch threshold as neither treatment nor time affected this measure. With regard to emotionality, castrated animals were significantly more reactive than the control animals at the 3 week but not 6 week interval. The data are interpreted as indicating that castration altered shock-induced aggression by preventing a maturational increase in such behavior. These behavioral alterations are compared to previously reported time-dependent changes in brain monoaminergic dynamics following gonadectomy. The conclusions support the concept of a necessary balance between catecholaminergic and serotonergic systems with regard to affective behavior.     

Adrenal activity in isolated mice and mice of different social status

The individual housing of male mice increases the incidence of aggressive behaviour. This study examines two suggestions, that isolation is stressful, and that it produces mice similar to dominant animals. Adrenal catecholamine content, plasma corticosterone, the weights of seminal vesicles, preputial and adrenal glands were measured in dominant, subordinate, isolated and group-housed mice. There was no evidence to suggest that isolation is stressful. Grouped mice had heavier adrenals than individually housed mice, and there was no difference in plasma corticosterone titre. In terms of adrenal weight and indices of gonadal function, the isolated mice were similar to dominant males. However, the literature indicates that isolated and dominant mice differ in their reactivity to stress. It was concluded that isolated male mice have physiological characteristics of their own.     

Influence of perinatal malnutrition and early handling on the pituitary-adrenal response to noxious stimuli in adult rats

A series of experiments examined the influence of perinatal malnutrition and infantile stimulation (preweaning handling) on the pituitary-adrenal response to novelty, electric shock and ether in adult rats. Neither early experience variable altered the magnitude or time course of the plasma corticosterone response to the combined stress of ether exposure and cardiac puncture. Although perinatal malnutrition did not change the magnitude of the adrenocortical response 15 min following a 1-min exposure to a novel test chamber alone or with 0.25 or 1.0 mA of scrambled electric shock, early handled subjects of both nutrition groups displayed lower corticoid elevations compared to nonhandled rats. Additionally, all subjects showed a lower corticoid elevation to the novel chamber without shock compared to the chamber plus electric shock, with females being able to display a differential corticoid response to the two shock levels. Perinatal malnutrition did not alter the magnitude and time course of the ACTH response to a 1-min exposure to a novel chamber alone or with ether. Thus, perinatal malnutrition does not appear to alter either the basal levels of ACTH and corticosterone or the response of these hormones following the stressors examined. Early handling modulated the response to novelty and electric shock but not ether, suggesting that the latter response is mediated by brain regions not influenced by infantile stimulation. Finally, the results of these studies indicate that the magnitude of the pituitary-adrenal response reflects different intensity levels of electric shock in female rats.     

Morphometrical variations of prolactin cells in response to prolonged and systemic administration of Met-enkephalin in female rats

Summary A stimulatory effect on prolactin secretion had been describe after acute and systemic administration of met-enkephalin, but the effects of this opioid after chronic administration has not been reported, and the response of mammotroph cells is not clear. As a complement to previous studies, a morphometric analysis (light and electron microscopy) was carried out on prolactin cells from female rats treated chronically with met-enkephalin. Clear features of cellular hyperactivity appeared after chronic and systemic administration of the opioid, and these persisted for two weeks. The changes consisted in increases of cellular, cytoplasmic and nuclear areas, volume and surface densities of the Golgi complex and rough endoplasmic reticulum, as well as the numbers of exocytotic figures. These morphological alterations were paralleled by an increase in serum prolactin levels as detected by RIA. It is concluded that the increase in the synthesis and secretory activity of prolactin cells following chronic and systemic administration of met-enkephalin is very similar to those observed after acute and intraventricular administration.     

Chronic restraint or variable stresses differently affect the behavior, corticosterone secretion and body weight in rats

Organisms are constantly subjected to stressful stimuli that affect numerous physiological processes and activate the hypothalamo-pituitary-adrenal (HPA) axis, increasing the release of glucocorticoids. Exposure to chronic stress is known to alter basic mechanisms of the stress response. The purpose of the present study was to compare the effect of two different stress paradigms (chronic restraint or variable stress) on behavioral and corticosterone release to a subsequent exposure to stressors. Considering that the HPA axis might respond differently when it is challenged with a novel or a familiar stressor we investigated the changes in the corticosterone levels following the exposure to two stressors: restraint (familiar stress) or forced novelty (novel stress). The changes in the behavioral response were evaluated by measuring the locomotor response to a novel environment. In addition, we examined changes in body, adrenals, and thymus weights in response to the chronic paradigms. Our results showed that exposure to chronic variable stress increased basal plasma corticosterone levels and that both, chronic restraint and variable stresses, promote higher corticosterone levels in response to a novel environment, but not to a challenge restraint stress, as compared to the control (non-stressed) group. Exposure to chronic restraint leads to increased novelty-induced locomotor activity. Furthermore, only the exposure to variable stress reduced body weights. In conclusion, the present results provide additional evidence on how chronic stress affects the organism physiology and point to the importance of the chronic paradigm and challenge stress on the behavioral and hormonal adaptations induced by chronic stress.     

Influence of isolation and training on fighting in mice with olfactory bulb lesions

Isolation-induced aggressive mice receiving total bilateral bulbectomy failed to fight after chronic training. Animals receiving sub-total olfactory bulbectomy were capable of being trained to attack but the latency to attack was increased. When mice were bulbectomized before being isolated they were incapable of attack regardless of training or completeness of the lesion. These results indicated that isolation influences aggressive behavior in bilaterally bulbectomized mice.     

Acute endocrine correlates of attack by lactating females in male mice: effects on plasma prolactin, luteinizing hormone and corticosterone levels

Immediately following defeat inflicted by lactating Rockland-Swiss (R-S) albino mice, adult R-S male mice exhibited significant reductions in circulating prolactin (PRL) and luteinizing hormone (LH), but not corticosterone (CORT). These results suggest that acute neuroendocrine responses to intersex competition may be as dramatic as those previously reported for intermale encounters.     

Effects of 2-deoxyglucose on plasma catecholamines in adult and aged rats

To examine the effects of aging on the responsiveness of the sympathetic-adrenal medullary system, I have measured plasma levels of norepinephrine (NE) and epinephrine (EPI) in adult (6 months old) and aged (24 months old) Fischer 344 male rats. Two days prior to testing, rats were surgically prepared with chronic tail artery catheters to permit remote sampling of blood in conscious, unrestrained animals. Following collection of basal blood samples, each rat received a single injection of 2-deoxyglucose (2-DG, 250 or 500 mg/kg, IP) and additional blood samples were collected 1, 2 and 4 hours later. 2-DG, a glucose analogue, stimulates a centrally mediated activation of the adrenal medulla and to a lesser extent the postganglionic sympathetic neurons. For purposes of analysis, data were excluded from animals which died within 4 hours after injection. Basal plasma levels of both catecholamines were similar in adult and aged rats. Administration of 2-DG was attended by significant and sustained increases in plasma NE and EPI in rats of both ages. A greater proportion of aged rats died following administration of 2-DG compared to adult rats. At the higher dose of 2-DG, plasma levels of NE were significantly higher in 6 month old rats at 1 and 2 hours post-injection. In contrast, plasma levels of EPI were significantly higher in 24 month old rats at 1 and 2 hours after administration of 250 mg/kg 2-DG and at 1 hour after administration of 500 mg/kg 2-DG. These findings indicated that the adrenal medullary response of aged rats to an intense and prolonged stressor is greater than that of adult rats. The attenuated plasma NE response of aged rats to 2-DG may be due to a lessor release of NE from the adrenal medulla and/or a diminished activation of postganglionic sympathetic nerves.     

Comparison of adrenal and foetal nigral grafts on drug-induced rotation in rats with 6-OHDA lesions

Summary Separate groups of rats with unilateral 6-OHDA lesions of the nigrostriatal pathway received intrastriatal foetal (E14) substantia nigra suspension grafts, intrastriatal postnatal (P22–25) adrenal medulla suspension grafts using either collagenaseor trypsin-based dissociation procedures, intraventricular adrenal medulla grafts, or remained with lesions alone. Rats with nigral or adrenal suspension grafts, but not rats with adrenal solid grafts, showed reduced apomorphine-induced rotation in comparison with lesion rats. The nigral graft group alone showed substantial reduction of amphetamine-induced rotation, and this was the only group manifesting good long-term graft survival. These results indicate that nigral and adrenal grafts do not have comparable mechanisms of functional action, and suggest that adrenal grafts can ameliorate apomorphine-induced rotation by a non-specific mechanism.     

Effects of 2-deoxyglucose on plasma catecholamines in adult and aged rats

To examine the effects of aging on the responsiveness of the sympathetic-adrenal medullary system, I have measured plasma levels of norepinephrine (NE) and epinephrine (EPI) in adult (6 months old) and aged (24 months old) Fischer 344 male rats. Two days prior to testing, rats were surgically prepared with chronic tail artery catheters to permit remote sampling of blood in conscious, unrestrained animals. Following collection of basal blood samples, each rat received a single injection of 2-deoxyglucose (2-DG, 250 or 500 mg/kg, IP) and additional blood samples were collected 1, 2 and 4 hours later. 2-DG, a glucose analogue, stimulates a centrally mediated activation of the adrenal medulla and to a lesser extent the postganglionic sympathetic neurons. For purposes of analysis, data were excluded from animals which died within 4 hours after injection. Basal plasma levels of both catecholamines were similar in adult and aged rats. Administration of 2-DG was attended by significant and sustained increases in plasma NE and EPI in rats of both ages. A greater proportion of aged rats died following administration of 2-DG compared to adult rats. At the higher dose of 2-DG, plasma levels of NE were significantly higher in 6 month old rats at 1 and 2 hours post-injection. In contrast, plasma levels of EPI were significantly higher in 24 month old rats at 1 and 2 hours after administration of 250 mg/kg 2-DG and at 1 hour after administration of 500 mg/kg 2-DG. These findings indicated that the adrenal medullary response of aged rats to an intense and prolonged stressor is greater than that of adult rats. The attenuated plasma NE response of aged rats to 2-DG may be due to a lessor release of NE from the adrenal medulla and/or a diminished activation of postganglionic sympathetic nerves.     

Effects of electrochemical stimulation of medial preoptic area on prolactin and luteinizing hormone release in old female rats

Summary Serum prolactin and LH levels in old constant estrous rats were higher than in old pseudopregnant rats. Electrochemical stimulation of the medial preoptic area in old constant estrous rats resulted in significant increases in serum concentration of prolactin and LH, and subsequent ovulation. Old pseudopregnant rats showed only a small increase in serum prolactin, no increase in serum LH and no ovulation. The high circulating levels of estrogen in old constant estrous rats, and the relative lack of estrogen and the presence of progesterone in the old pseudopregnant rats, may account for the differences observed in response of the medial preoptic area to electrochemical stimulation.Aided in part by NIH research grants CA 10771 and AM 4784.