Dopaminergic inhibition of striatal acetylcholine release after 6-hydroxydopamine

European Journal of Pharmacology
R G MacKenzieM J Zigmond

Abstract

Field stimulation increased tritium efflux from rat striatal slices preincubated with [3H]choline, an index of acetylcholine release. When stimulated at low frequency (1 Hz for 2 min), nomifensine (10 microM) reduced acetylcholine release, while at high frequency (8 Hz for 1 min), sulpiride (1 microM) increased release. After 6-hydroxydopamine-induced damage to dopamine neurons, these effects were reduced but the extent of the depletion necessary to block the drug effects increased with the passage of time. Up-regulation of dopamine D-2 receptors seen at 2 months was not detected unless dopamine depletion was very large (90%). These findings indicate that dopamine, acting at the dopamine D-2 receptor, normally exerts an inhibitory influence over acetylcholine release in striatum, that after partial injury the dopaminergic influence over acetylcholine release can recover with time, and that the recovery involves processes other than changes in the number of D-2 receptors.

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