There is now considerable evidence that opioid drugs can influence the activity of brain dopamine systems. Furthermore, they can modify behavioral effects of drugs that act via brain dopamine systems. such as amphetamine and cocaine, in ways that might influence potential for abuse. The rat unilateral rotational model, produced by lesioning the nigrostriatal tract on one side of the brain, affords a means of studying and quantifying drug interactions with the nigrostriatal dopaminergic system. This model will be used as a behavioral indicator of how opioid drugs modify a dopaminergically-mediated effect of amphetamine and cocaine. Systematic experiments, using receptor-selective opioid agonists and antagonists, will be performed to determine: a) if enhancement by morphine of turning induced by amphetamine and cocaine is mediated by mu-opioid receptors; b) if activation of delta- and kappa- opioid receptors influences the behavioral response to amphetamine and cocaine. Opioid drugs can, under some circumstances, differentially modify behavioral and neurochemical effects of amphetamine and cocaine. The proposed comparison of the two drugs will provide further evidence of similarities or differences in the opioid modulation of dopaminergically-mediated of-behavioral effects of these drugs.
