Does GABA act through dopaminergic/cholinergic interaction in the regulation of higher environmental...

Acute exposure of adult male albino rats to higher ambient temperature (40 degrees C) for 2 h significantly increased body temperature (BT). Administration of either bicuculline (1 mg/kg, i.p.), a GABA antagonist, or physostigmine (0.1 mg/kg, i.p.), an inhibitor of acetylcholinesterase, significantly increased BT of normal and heat-exposed rats. Treatment with muscimol (1 mg/kg, i.p.), a GABA agonist, produced hypothermia in normal rats and prevented an increase in BT of heat-exposed rats. The dopamine agonist, L-dopa (100 mg/kg, p.o.) along with carbidopa (10 mg/kg, p.o.) reduced BT of normal rats. Further, the bicuculline-or physostigmine-induced enhancement of BT in normal and heat-exposed rats was potentiated when both drugs were administered concomitantly. But this potentiating effect remained unaltered when dopamine antagonist haloperidol (1 mg/kg, i.p.) was administered along with bicuculline and physostigmine. Treatment with atropine (5 mg/kg, i.p.), a cholinergic antagonist, abolished the hyperthermic effect of bicuculline but potentiated the hypothermic effect of muscimol either at 28 degrees C or at 40 degrees C. Bicuculline-induced hyperthermia was attenuated at normal or higher temperature by pretreatment with L-dopa + carbidopa. The administration of L-dopa + carbidopa either abolished or reduced the hyperthermic effect of physostigmine at room temperature or at higher ambient temperature. These results suggest that (a) GABAergic, cholinergic and dopaminergic systems are involved in thermoregulation, (b) exposure to high environmental temperature may inhibit central GABAergic activity which activates the cholinergic system without affecting the dopaminergic system and raises BT, (c) central dopaminergic and GABAergic systems act independently through the modulation of cholinergic activity in the regulation of BT under normal ambient temperature.