Effects of response contingent and noncontingent cocaine injection on hypothalamic-pituitary-adrenal activity in rhesus monkeys

Earlier studies of cocaine's effects on the hypothalamic-pituitary-adrenal (HPA) axis used nonresponse-contingent designs in which the investigator de termined dose, timing, and route of administration. It is important to eval uate whether "control" over cocaine delivery is a significant determinant o f cocaine's HPA axis effect. This study measured cocaine's effects on plasm a adrenocorticotropic hormone and cortisol, using nonresponse-contingent in jections followed later by response-contingent cocaine delivery. In additio n, the effects of cocaine history on the HPA response to a noncontingent in jection of 1 mg/kg of cocaine were measured. HPA effects of corticotropin-r eleasing hormone (CRF) were also measured. Male and female rhesus monkeys, with surgically placed venous catheters, were tested in their home cages. U p to 13 injections of saline and cocaine (0.01-, 0.03-, 0.1-, and 0.3-mg/kg /injection) were administered at 10-min intervals (nonresponse-contingent c ondition) and on a fixed ratio 30, time out 10-min schedule of reinforcemen t. Overall, cocaine delivered response contingently produced larger, more d ose-dependent HPA responses than did noncontingent delivery. The HPA respon se to a 1 mg/kg cocaine infusion in cocaine-naive monkeys was not predictiv e of the HPA effect of this dose subsequent to acquisition of cocaine self- administration. Overall, male monkeys had larger HPA responses to cocaine t han did female monkeys. Finally, the HPA effects of CRF were significantly correlated with those of targe cocaine doses delivered nonresponse continge ntly, but not with response-contingent administration.