Elsevier

Neuroscience

Volume 19, Issue 4, December 1986, Pages 1109-1117
Neuroscience

In vivo release of [3H]γ-aminobutyric acid in the rat neostriatum—II. Opposing effects of D1 and D2 dopamine receptor stimulation in the dorsal caudate putamen

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Abstract

The effects of several dopaminergic agonists and antagonists on the spontaneous release of [3H]γ-aminobutyric acid were investigated in the dorsal striatum of halothane-anaesthetized rats. A push pull cannula was implanted and the tissue was superfused continuously with a physiological medium containing [3H]glutamine, the precursor of [3H]GABA. Drugs were added to the superfusion medium. 2-Amino,6,7-dihydroxy,1,2,3,4-tetrahydro-naphtalene (ADTN, a mixed Dl and D2 receptor agonist) andd-amphetamine (a drug that enhances the release of endogenous dopamine) increased the release of3H-GABA. The effect of ADTN was blocked by a D1 antagonist [R−( + ),8-chloro,7-hydroxy,2,3,4,5,-tetrahydro,3-methyl,5-phenyl,1-H,3-benzazepine (SCH 23390)] but not by a D2 antagonist (S-sulpiride). Furthermore the stimulation of D1 receptors either by 2,3,4,5-tetrahydro,7,8-dihydroxy, 1-phenyl, 1-H,3-benzazepine or byd-amphetamine in the presence of S-sulpuride also enhanced the release of [3H]GABA. On the other hand, a selective D2 receptor agonist (3-(2-(N-3-hydroxyphenylethyl)N-propylamino)ethyl-phenol) decreased the release of [3H]GABA. This effect was blocked in the presence of S-sulpiride. By itself the D1 receptor antagonist (SCH 23390) decreased the release of [3H]GABA whereas the D2 receptor antagonist (S-sulpinde) had no effect.

It was concluded that stimulation of D1 and D2 receptors produces opposing effects on the spontaneous release of [3H]GABA in the dorsal striatum. Stimulation of D1 receptors facilitates the release of [3H]GABA whilst stimulation of D2 receptors inhibits it. The effect of D1 receptor stimulation appears to be predominant, and endogenous dopamine may activate tonically the release of GABA through these receptors in our experimental conditions. The functional implications of these observations are discussed.

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