Changes of body temperature and thermoregulatory responses of freely moving rats during GABAergic pharmacological stimulation to the preoptic area and anterior hypothalamus in several ambient temperatures

Action of γ-aminobutyric acid (GABA) in the preoptic area and anterior hypothalamus (PO/AH) has been implicated to regulate body temperature (Tb). However, its precise role in thermoregulation remains unclear. Moreover, little is known about its release pattern in the PO/AH during active thermoregulation. Using microdialysis and telemetry techniques, we measured several parameters related to thermoregulation of freely moving rats during pharmacological stimulation of GABA in normal (23 °C), cold (5 °C), and hot (35 °C) ambient temperatures. We also measured extracellular GABA levels in the PO/AH during cold (5 °C) and heat (35 °C) exposure combined with microdialysis and high performance liquid chromatography (HPLC). Perfusion of GABAA agonist muscimol into the PO/AH increased Tb, which is associated with increased heart rate (HR), as an index of heat production in all ambient temperatures. Although tail skin temperature (Ttail) as an index of heat loss increased only under normal ambient temperatures, its response was relatively delayed in comparison with HR and Tb, suggesting that the increase in Ttail was a secondary response to increased HR and Tb. Locomotor activity also increased in all ambient temperatures, but its response was not extraordinary. Interestingly, thermoregulatory responses were different after perfusion of GABAA antagonist bicuculline at each ambient temperature. In normal ambient temperature conditions, perfusion of bicuculline had no effect on any parameter. However, under cold ambient temperature, the procedure induced significant hypothermia concomitant with a decrease in HR in spite of hyperactivity and increase of Ttail. It induced hyperthermia with the increase of HR but no additional change of Ttail in hot ambient temperature conditions. Furthermore, the extracellular GABA level increased significantly during cold exposure. Its release was lower during heat exposure than in a normal environment. These results indicate that GABA in the PO/AH is an important neurotransmitter for disinhibition of heat production and inhibition of heat loss under cold ambient temperature. It is a neurotransmitter for inhibition of heat production under hot ambient temperature.