The Effect of Long‐Term Castration on the Neuronal and Physiological Responses to Acute or Repeated Restraint Stress: Interactions with Opioids and Prostaglandins

Sixty min supine restraint stress induced a marked, but transient, hypothermic response in intact male rats, which tended to recover towards pre‐stress levels or slightly overshoot during the later stages of restraint. Castration reduced the initial hypothermia but increased overshoots. Baseline (pre‐stress) core temperature was also higher in castrated than intact rats, but the reduction in stress‐induced hypothermia was still present even when this difference had been taken into account. The hypothermic response was not altered during the course of 10 sessions of daily repeated restraint in either intact or castrated rats. Castration did not alter cardiac responses to restraint. Both intact and castrated rats showed marked tachycardia during the initial 12 min of restraint, followed by a gradual fall towards baseline values. Repeated restraint accentuated the second phase of the cardiac response, without modifying the initial tachycardia, in both intact and castrated animals. The response of blood corticosterone levels to the first period of restraint was unaltered by castration but the attenuation observed after 10 sessions of stress was more complete in castrated rats. The neuronal c‐fos response 60 min after the last of the series of repeated restraints was less in the hypothalamic paraventricular nucleus, medial amygdala, and locus coeruleus compared with that following the first session, but not in the lateral septum or the bed nucleus of the stria terminalis. Castration did not change the c‐fos profile following the same number of restraint sessions. Castration depleted completely the vasopressinergic innervation in the lateral septum, diagonal band of Broca and medial amygdala. Five mg/kg naloxone i.p. prior to the onset of stress resulted in persistent hypothermic responses throughout the stress period in intact males. This was reduced in castrated rats. Blockade of prostaglandins synthesis by 12 mg/kg indornethacin i.p. 3 h prior to stress had little effect on hypothermic stress responses. The results of these experiments suggest that an androgen‐dependent process, possibly AVP‐containing systems in the forebrain, may regulate both baseline and stress‐induced levels of core temperature and have selective effects on components of the response to stress, including restraint‐induced hypothermia and the adaptation of corticoid responses to repeated restraint. Steroid‐dependent opioid systems may also be implicated in the hypotherrnic response to restraint stress.