The aim of the proposed research is to elucidate the neuronal mechanisms underlying the behavioral effects of indoleamine (LSD-like) and phenylalkylamine (mescaline-like) hallucinogens, central nervous system (CNS) stimulants (amphetamine, cocaine), and drugs of abuse which appear to have both hallucinogenic and stimulant properties (MDA, MDMA). While our primary focus will be on serotonin (5-HT), we will also be concerned with other, monoaminergic transmitter systems and with sub-systems involving putative multiple receptor subtypes. Our principle behavioral method will be drug discrimination but, when the nature of the problem or technical considerations demand it, other assays will be used; for example, disruption of schedule-controlled, operant responding or assessment of """"""""conflict"""""""" (behavior simultaneously maintained by food and suppressed by painful stimuli). The neural substrates of drug effects in intact, behaving organisms (rats) will be studied both pharmacologically (indirectly) and physiologically (directly). In pharmacological experiments: 1) Groups of animals will be trained to discriminate relatively low doses of various drugs of interest (from saline or, in some instances, from each other) and be tested with recently developed, specific receptor subtype agonists (""""""""substitution"""""""" or """"""""generalization"""""""" tests) or antagonists (""""""""combination"""""""" tests); 2) independent groups of animals will be trained to discriminate subtype agonists and be tested with hallucinogenic, stimulant and hallucinogenic/stimulant drugs of abuse as well as with receptor antagonists. In order to determine sites of drug actions more precisely, direct, """"""""physiological"""""""" interventions will also be used; that is, 1) drugs will be administered intracerebrally; 2) brain areas which are thought to contain monoaminergic neuronal cell bodies (raphe, nucleus accumbens, caudate nucleus, locus ceruleus, etc.) will be chemically-lesioned with specific neurotoxins; and 3) the effects of electrical stimulation of different brain regions will be compared to the stimulation caused by systemically administered drugs.
Showing the most recent 10 out of 23 publications
