Effects of catecholamine depleting drugs and d-amphetamine on self-stimulation of the substantia nigra and locus coeruleus.
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.
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D006892:Hydroxydopamines / Q000494:pharmacology; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D012653:Self Stimulation / Q000187:drug effects*; D013378:Substantia Nigra / Q000502:physiology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors
D002395:Catecholamines; D006892:Hydroxydopamines; D012110:Reserpine; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D003913:Dextroamphetamine