Rat substantia nigra pars reticulata neurones are tonically inhibited via GABAA, but not GABAB, receptors in vitro.
Extracellular single unit recordings were made from substantia nigra pars reticulata (SNr) neurones in slices of rat brain. Cells fired spontaneous action potentials at 11.4 +/- 0.8 Hz. The GABAA receptor agonist isoguvacine (1-10 microM) reduced firing rate in a concentration-dependent manner [50% of maximal inhibition (IC50) with 3.2 microM], as did the GABAB agonist baclofen (0.3-10 microM; IC50 1.4 microM). The GABAA antagonist bicuculline (30 microM) not only blocked the action of isoguvacine, but also increased the basal firing rate to 187.5 +/- 12.6% of control. The GABAB antagonist CGP 55845A (0.1 microM), while blocking the inhibitory action of baclofen, was without effect on spontaneous firing rate, as was strychnine (10 microM), the antagonist of glycine and taurine, and also Met-enkephalin (10 microM). Tiagabine (50 microM), the blocker of GABA uptake, caused an inhibition of firing which could be reversed with bicuculline (30 microM) but not CGP 55845A (1 microM). We conclude that the firing rate of SNr neurones is under tonic inhibition by GABA in vitro, which can be relieved by antagonists of GABAA, but not GABAB receptors, and enhanced by blockade of GABA reuptake. The source of this GABA tone is likely to be from recurrent axon collaterals of SNr neurones themselves.
Rick
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CE
Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, UK.
Lacey
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MG
D000818:Animals; D004744:Enkephalin, Methionine / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009557:Nipecotic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000145:classification / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000078308:Tiagabine
D018755:GABA Agonists; D018756:GABA Antagonists; D009557:Nipecotic Acids; D018079:Receptors, GABA; D004744:Enkephalin, Methionine; D000078308:Tiagabine