INTERACTIONS BETWEEN CORTICOTROPIN-RELEASING FACTOR AND ENDOGENOUS OPIATES ON THE CARDIOACCELERATOR, HYPOTHERMIC, AND CORTICOID RESPONSES TO RESTRAINT IN THE RAT

These experiments investigated the effect of either systemic opiate blockade by naloxone (5 mg/kg) or intracerebroventricular CRF (250 pmol), or the two treatments combined, on physiological and endocrine responses of male rats to two types of stress: restraint by itself (representing a psychological stress), and restraint combined with a tail clip (representing an additional mild physical nociceptive stress). Rats were restrained in a plastic container for 15 min, with or without a tail clip. Heart rate, body temperature, and serum corticosterone were measured. The first experiment showed that restraint induced marked tachycardia, maximal at 5 min, and declining thereafter. There was also a pronounced hypothermia, maximal at 10 min, and serum corticosterone was elevated 10 min after the end of the period of restraint. The presence of a tail clip increased the cardioaccelerator response, but had no effect on hypothermia. Naloxone had no effect on heart rate during restraint or on postrestraint corticosterone, but accentuated hypothermia. The effects of naloxone occurred independently of the presence of a tail clip. A subsidiary experiment showed that rats transferred to an unfamiliar cage showed a marked hyperthermic response, as described by others. The second experiment showed that CRF (250 pmol ICV) did not modify the tachycardiac response to restraint, but reduced hypothermia. This also occurred irrespective of the presence of a tail clip. The third experiment investigated the interaction between naloxone and CRF, and showed that the ameliorative effects of ICV CRF on restraint-induced hypothermia were prevented by systemic naloxone, but that neither tachycardia nor corticosterone responses were altered. Together these experiments show that there is a differentiated response to stressors made up of different components; that opiate blockade and CRF have selective effects on the hypothermic response to restraint; and that the effect of CRF may be mediated by endogenous opiates.