In the proposed research we plan to continue experiments that will elucidate the neurobehavioral bases of the effects of the CNS stimulants, i.e., cocaine and d-amphetamine, and opioids on rewarding brain stimulation. Our previous work has indicated that all drugs that increase the sensitivity of animals to this stimulation are either abuse substances or have the potential for abuse. The opioids that we will study are morphine, heroin, the mixed agonist-antagonist pentazocine, as well as the kappa agonists ethylketocyclazocine and U-50,488. We will study the effects of both opioid and dopaminergic blocking agents on the effect of these compounds. We will compare their effects in animals with electrodes in various brain sites. Further we will attempt to determine the mechanisms involved in the potentiation of the reward threshold lowering effect with the mixed agonist-antagonists by the antihistaminic tripelennamine (this combination has the street name of """"""""T's and Blues""""""""). By means of the 2-deoxyglucose method we will determine the effects of some of the above drugs on local cerebral glucose utilization during rewarding brain stimulation. We also will use 6-hydroxydopamine as a tool to deplete specific dopaminergic nuclei in order to further elaborate the relationship between dopaminergic and opiate systems in the mediation of the observed effect of opioids and CNS stimulants. Using brain-stimulation escape as a method for the study of the analgesic effects of drugs we will attempt to determine whether or not the observed potentiation of the analgesic action of morphine by amphetamine is unique for amphetamine or will other catecholaminergic agents will also potentiate the analgesic effect of morphine. Of practical importance is whether or not d-amphetamine would potentiate the analgesic response of a drug with less analgesic efficacy than morphine. By using the 2-deoxyglucose method we will compare the effects of nociceptive stimulation to the mesencephalic reticular formation after morphine, naloxone, and d-amphetamine plus morphine in combination. It is through these experiments that we hope to contribute to our understanding of why abuse substances are rewarding.
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