Continuing research on this project is predicated on the assumption that valuable basic information, of long-term relevance both to drug abuse and more generally to understanding of neurotransmitter control of behavior, can be gotten from studies of similarities, differences, and interactions in the behavioral effects of drugs of abuse and of drugs affecting brain neurotransmitter activity. A primary focus will be on the development of a base of knowledge of the role of serotonin (5-HT) neurotransmission in the control and modulation of behavior, and of the participation of 5-HT systems in mediation of the action of certain drugs of abuse. Three general types of experiments will be done with schedule- controlled behavior of squirrel monkeys. One series of experiments will be concerned with the behavioral effects (including analgesic properties) of compounds with agonist and antagonist properties at the putative 5-HT-l and 5-HT-2 subtypes of the serotonin receptor. These compounds 1- naphthylpperazine (5-HT-l agonist, but 5-HT-2 antagonist); 1-(2- methoxyphenyl)piperazine (highly selective 5-HT-l agonist); and p- aminophenylethyl-m-TFMPP (a selective 5-HT-lA agonist). A second series of experiments will continue studies on the behavioral effects of the phenylisopropylamine hallucinogenic drugs 4-bromo-2,5-dimethoxyamphetamine (DOB) and 4-methyl- 2,5dimethoxyamphetamine (DOM), and will evaluate the extent to which the effects of these drugs can be blocked with antagonists of serotonin and of other neurotransmitters. Finally, experiments will be done to characterize interactions in the behavioral effects of opioid agonists and antagonists with hallucinogenic drugs such as DOM. Previous work in this laboratory and elsewhere has shown that the opioid antagonist naloxone markedly enhances the behavioral effects of hallucinogens, and there are suggestions that opioid agonists such as morphine have the opposite effect. In addition to morphine and naloxone, other drugs with differing affinities for the mu- and kappa-opioid receptor subtypes will be studied.
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