REINFORCING EFFECTS IN RHESUS MONKEYS

$0P50FY2002DANIH

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

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Abstract

DESCRIPTION: (provided by applicant) This project uses monkeys with chronically indwelling intravenous catheters that can be used for passive drug administration, active drug self-administration and to take blood samples. When blood samples are taken, they will be analyzed for ACTH and cortisol levels. The goals of this project are first to determine the effects of acute administration of opioid drugs on the HPA axis, and to determine if increases in HPA axis activity can be used to measure acute naloxone-precipitated dependence to mu and kappa opioids. If so, the parameters of time following drug administration and the interval between drug injections will be evaluated to determine the role they play in the development of acute dependence. Second, the ability of breathing 5 percent CO2 and administration of 13 carboline ethyl ester to provoke a stress response as indicated by increases in ACTH will be measured. The ability of morphine and diazepam to attenuate each of these stress responses will be determined and compared. Morphine dependence will be produced in these animals and evidence for protracted abstinence will be looked for as a hyporeactivity of the HPA axis to 5 percent CO2 and 13CCE administration. Such a protracted abstinence reaction to restraint stress has been demonstrated in rats. The effects of self-administered opioids on the HPA axis will be established and compared with the effects previously observed with passive opioid administration. These effects of self-administered opioids on plasma levels of ACTH and cortisol will also be determined in animals with high "basal" levels of ACTH and cortisol as a result of either presession administration of 13CCE or opioid withdrawal. A procedure whereby demand functions are obtained in single 2-hr sessions will be used to determine if the elasticity of the demand function for short-acting opioid is decreased during opioid withdrawal. Finally, evaluation of the reinforcing effects of novel opioids as submitted by government agencies, academic, or industrial laboratories will continue.

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