EFFECTS OF CATECHOLAMINE DEPLETING DRUGS AND D-AMPHETAMINE ON SELF-STIMULATION OF SUBSTANTIA NIGRA AND LOCUS COERULEUS

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 204  (3) , 592-605
Abstract
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. A dose of .alpha.-methyltyrosine which 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 [1-phenyl-3-(2-thiazolyl)-2-thiourea] 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. 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.