HYPOTHERMIA INDUCED BY INFUSION OF METHIONINE SULFOXIMINE INTO THE DORSAL RAPHE NUCLEUS OF THE RAT - INVOLVEMENT OF 5-HT(1A) AND GABA(B) RECEPTORS

L-Methionine-D,L-sulfoximine (MSO) (25 mug) infused locally into the dorsal raphe nucleus (DRN) induced a progressive decrease in body temperature in conscious restrained rats kept at an ambient temperature of 23-degrees-C. Pretreatment with (+/-)-pindolol (3 mg/kg s.c.) significantly attenuated MSO-induced hypothermia, but pretreatment with ketanserin (0.5 mg/kg i.p.) did not alter either the magnitude or the time course of the decrease in body temperature after intra-DRN infusion of MSO. Local accumulation of gamma-aminobutyric acid (GABA) after infusion of gamma-vinylGABA (10 mug) and (+/-)-nipecotic acid (6 mug) inhibited MSO-induced hypothermia. Blockade of GABA(A) receptors by infusion of (-)-bicuculline (25 ng) had no effect on the decrease in body temperature elicited by MSO, but blockade of GABA(B) receptors by infusion of 2-OH-saclofen (13.3 ng) significantly attenuated MSO-induced hypothermia. In conclusion, local infusion of MSO into the DRN must have slowed down the rate of 5-HT turnover in serotonergic neurons and decreased the release and synthesis of GABA. 5-HT1A somato-dendritic autoreceptors and GABA(B) postsynaptic receptors both appear to be involved in these neurocytochemical processes leading to hypothermia.