Effects of catecholamine depleting drugs and d-amphetamine on self- stimulation of the substantia nigra and locus coeruleus

BR Cooper, RJ Konkol and GR Breese

6-Hydroxydopamine treatments which preferentially depleted either norepinephrine or dopamine were used to define the importance of these transmitter systems in the behavioral alterations produced by catecholamine synthesis inhibitors and d-amphetamine on self- stimulation of the locus coeruleus and substantia nigra. After chronic reduction of brain dopamine, an acute depression of self-stimulation of both the locus coeruleus and substantia nigra occurred. Preferential depletion of norepinephrine with 6-hydroxydopamine did not result in a significant decrease in self-stimulation of locus coeruleus or substantia nigra. However, a dose of alpha-methyltyrosine wihch had no effect in control rats or in rats with brain norepinephrine depleted caused a significant reduction in responding at both electrode placements in animals depleted of brain dopamine. Administration of U- 14,624 affected neither substantia nigra nor locus coeruleus self- stimulation, even though it produced an additional 70% depletion of norepinephrine. When d-amphetamine sulfate was given to 6- hydroxydopamine-treated rats, the facilitation of self-stimulation produced by this compound was significantly attenuated in rats with prior depletion of brain dopamine. Depletion of brain norepinephrine did not affect the actions of d-amphetamine on self-stimulation. In other experiments, the actions of d-amphetamine to increase self- stimulation of animals pretreated with reserpine was found to be antagonized by alpha-methyltyrosine but not by U-14,624. Results suggest that drugs can alter self-stimulation of a site in brain anatomically associated with noradrenergic neural pathways and self- stimulation of a site primarily associated with dopaminergic pathways in a similar manner. These data also provided evidence for the involvement of dopamine fibers in the pharmacological actions of d- amphetamine, reserpine and alpha-methyltyrosine.

Volume 204, Issue 3, pp. 592-605, 03/01/1978
Copyright © 1978 by American Society for Pharmacology and Experimental Therapeutics

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