title: D(2)-like dopamine receptors differentially regulate unitary IPSCs depending on presynaptic GABAergic neuron subtypes in rat nucleus accumbens shell.
abstract: In the nucleus accumbens (NAc), a medium spiny (MS) neuron receives GABAergic inputs from two major sources: fast-spiking (FS) neurons and other, adjacent MS neurons. These two types of inhibitory synapses are considered to play different roles in output activities, i.e., FS→MS connections suppress output from the NAc whereas MS→MS connections contribute to lateral inhibition. In the present study, we focused on the electrophysiological properties of unitary inhibitory postsynaptic currents (uIPSCs) obtained from MS→MS connections and FS→MS connections and examined the effects of quinpirole, a dopamine D(2)-like receptor agonist, on uIPSCs with multiple whole cell patch-clamp recording. Application of quinpirole (1 μM) reliably suppressed the amplitude of uIPSCs by 29.6% in MS→MS connections, with increases in paired-pulse ratio and failure rate. The suppressive effects of quinpirole on uIPSCs were mimicked by 1 μM PD128907, a D(2/3) receptor agonist, whereas quinpirole-induced suppression of uISPCs was blocked by preapplication of 1 μM sulpiride or 10 μM nafadotride, both D(2/3) receptor antagonists. On the other hand, quinpirole (1 μM) had divergent effects on FS→MS connections, i.e., quinpirole increased uIPSC amplitude in 38.1% of FS→MS connections and 23.8% of FS→MS connections were suppressed by quinpirole. Analysis of coefficient of variation in uIPSC amplitude implied the involvement of presynaptic mechanisms in quinpirole-induced effects on uIPSCs. These results suggest that activation of D(2)-like receptors facilitates outputs from MS neurons in the NAc by reducing lateral inhibition during a dormant period of FS neuron activities.
authors: Department of Pharmacology, Nihon University School of Dentistry, Tokyo, Japan.
authors: Shuntaro
authors: S
authors: Kohnomi
authors: Noriaki
authors: N
authors: Koshikawa
authors: Masayuki
authors: M
authors: Kobayashi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D058787:GABA-A Receptor Antagonists; D059330:GABAergic Neurons / Q000145:classification / Q000166:cytology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009434:Neural Pathways / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013997:Time Factors
chemical_list: D015259:Dopamine Agents; D058787:GABA-A Receptor Antagonists; D018727:Muscarinic Antagonists; D017448:Receptors, Dopamine D2; D001285:Atropine; D001640:Bicuculline