Dopamine D2 receptor mediated presynaptic inhibition of striatopallidal GABA(A) IPSCs in vitro.
The modulation of GABA release within the globus pallidus (GP) by dopamine was studied using whole-cell patch clamp recordings from visually identified neurones. In sagittal slices, single shock electrical stimulation in the striatum evoked GABA(A) inhibitory postsynaptic currents (IPSCs), which were inhibited by dopamine in a dose-dependent manner (0.3-30 microM) with an IC(50) value of 0.7 microM. The inhibition was accompanied by an increase in paired pulse facilitation, indicative of a presynaptic effect. In coronal slices, stimulation within the GP adjacent to the recording site evoked GABA(A) IPSCs which were relatively unaffected by dopamine indicating the lack of modulation of GABA release from terminals of local GP axon collaterals. No consistent changes in holding current, membrane potential, firing rate or the frequency of spontaneous IPSCs was observed.Tetrodotoxin-resistant miniature (m)IPSCs were recorded in chloride-loaded cells. Dopamine (3-30 microM) reduced the frequency of mIPSCs, but was without effect on mIPSC amplitude, confirming a presynaptic effect. The addition of the "D2 like" agonist quinpirole (3 microM), but not the "D1 like" agonist SKF 38393 (10 microM), mimicked these effects. The "D2 like" antagonist sulpiride (10 microM), while having no effect alone, blocked the action of dopamine. In contrast the dopamine D4 selective antagonist L745, 870 (1 microM) or D1 antagonist SCH 23390 (10 microM) were without effect. These results indicate that dopamine acts on presynaptic D2 receptors on striatopallidal terminals to reduce the release of GABA in the GP. Attenuation of this mechanism following the depletion of dopamine may contribute to the changes in GP neuronal activity observed in animal models of Parkinson's disease.
Cooper
A J
AJ
Department of Pharmacology, Division of Neuroscience, The Medical School, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Stanford
I M
IM
D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D017661:Receptors, Presynaptic / Q000187:drug effects*
D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D017661:Receptors, Presynaptic; D004298:Dopamine