In vivo voltammetry is a novel research tool in neuroscience which allows dopamine (DA), norepinephrine (NE), and serotonin release to be measured in discrete brain regions of freely moving animals. The objective of this proposal is to measure changes in DA release during intravenous (i.v.) self-administration of the psychomotor stimulant drugs, d-amphetamine, cocaine and methylphenidate, and the opiates, heroin and methadone. The underlying hypothesis upon which these studies are based is that the mesolimbic DA projection is important for the acquisition and maintenance of stimulant and perhaps opiate self-administration. For each drug, DA release will be measured in the nucleus accumbens, olfactory tubercle and striatum. We propose to determine the extent to which i.v. self-administration of stimulant and opiate drugs increases DA release in each of these brain regions and, if so, to correlate these increases with the pattern and rate of operant responding for each drug. Specifically, we propose to: (a) determine if animals work to maintain a constant increased level of DA release in one or more of these structures regardless of the dose of drug per infusion and the rate of operant responding; (b) determine if differences exist between the drugs in the extent to which they increase DA release at doses that maintain approximately the same level of operant responding; and (c) identify the regions within DA-rich regions of the forebrain where DA release may be more critically invovled in regulating self-administration of these drugs. The long-term objectives of this proposal are to provide detailed, quantitative information concerning the relationships that exist between DA release in forebrain areas in i.v. self-administration of stimulants and opiates and to achieve a better understanding of the neuronal mechanisms involved. The proposed studies will also lay the foundation for an in vivo method of measuring DA release during self-administration of other drugs of abuse.
