Effects of GABA agonists and antagonists on temperature sensitive neurones in the rat hypothalamus

1. Extracellular recordings were obtained from 94 warm-sensitive, 6 cold-sensitive and 117 temperature-insensitive neurones in slices of the hypothalamic medial preoptic area of rats, to determine the effect of the GABA(A) agonist muscimol, the GABA(A) antagonist bicuculline, the GABA(B) agonist baclofen and the GABA(B) antagonist phaclofen on tonic activity and temperature sensitivity. 2. Muscimol and baclofen dose-dependently inhibited the tonic activity of 69% (36/52) and 97% (36/37) of the hypothalamic neurones, respectively, regardless of their type of thermosensitivity. In contrast, the GABA(A) antagonist bicuculline increased the tonic activity of the majority of neurones (58/83), while the GABA(B) antagonist phaclofen increased neuronal activity only in the high dose of 100 mu M. 3. The temperature sensitivity of hypothalamic neurones was only changed by ligands of GABA(B) receptors, and this effect was restricted to warm-sensitive neurones. The temperature coefficient (TC) was significantly increased by the GABA(B) agonist baclofen (Delta>TC = 0.69 +/- 0.11 imp s(-1) degrees C-1, P<0.01, n = 18). In contrast, the GABA(B) antagonist phaclofen (10 mu M) decreased the temperature sensitivity (Delta TC = -0.67 +/- 0.09 imp s(-1) degrees C-1, P<0.01, n = 10) in doses which did not affect tonic activity. 4. The increase in temperature sensitivity due to the GABA(B) agonist baclofen was significantly enhanced by co-perfusion of the GABA(A) antagonist bicuculline, indicating an interaction of GABA(A) and GABA(B) receptor-mediated mechanisms with regard to neuronal thermosensitivity. 5. The results suggest that neurones in the medial preoptic area are subject to GABA-mediated tonic inhibition resulting in modulation of tonic activity and temperature sensitivity of warm-sensitive neurones possibly involved in the control of body temperature. The data support the hypothesis that the hypo- or hyperthermic, action of an endogenous substance is related to its effect on the thermosensitivity rattler than on tonic activity of hypothalamic neurones.