A powerful GABA(B) receptor-mediated inhibition of GABAergic neurons in arcuate nucleus

WE combined histofluorescence with in situ hybridization to identify GABAer gic neurons in the arcuate nucleus (ARC) following electrophysiological rec ording, using GAD(65) as a marker. Intracellular recordings 91 were made in hypothalamic slices prepared from ovariectomized guinea pigs. Over 90% of ARC neurons tested with the GABA(B) receptor agonist baclofen responded wit h a membrane hyperpolarization or an outward current. The hyperpolarization was dose dependent, and the GABA(B) receptor antagonist CGP 35,348 produce d a rightward shift in the agonist dose-response curve. Agonist potency was lower, and the efficacy greater, in GAD-positive neurons. The use of this novel technique for identifying GABAergic neurons thus reveals differences in the pharmacodynamics of GABA(B) receptor activation between GABAergic an d non-GABAergic ARC neurons. (C) 1999 Lippincott Williams & Wilkins.