Brain research bulletin
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Brain research bulletin · Apr 1998
Postsynaptic integration of cholinergic and dopaminergic signals on medium-sized GABAergic projection neurons in the neostriatum.
The effects of cholinergic drugs and the interaction between cholinergic and dopaminergic compounds were studied on electrically evoked [3H]gamma-aminobutyric acid (GABA) overflow in slices of the rat neostriatum. Slices were prepared and loaded with [3H]GABA in the presence of beta-alanine and then superfused with Krebs-bicarbonate buffer containing aminooxyacetic acid and nipecotic acid to inhibit GABA uptake and metabolism, respectively. The nonselective muscarinic agonist oxotremorine (0.1-10 microM) increased the release of [3H]GABA and the selective M1 receptor agonist McN-A-343 (0.1-10 microM) exerted similar effect. ⋯ McN-A-343 and sulpiride also increased the KCl-induced [3H]GABA overflow from superfused neostriatal slices and tetrodotoxin (1 microM) did not affect these stimulations. These data indicate that the release of GABA in the neostriatum is under the control of M1 stimulatory and M3 inhibitory muscarinic receptors. Dopamine, which exerts inhibition on GABA release via D2 receptors, may counteract the M1 facilitation, and M1 and D2 receptors involved in the cholinergic-dopaminergic interaction may be located postsynaptically on medium-sized spiny GABAergic projection neurons.