Involvement of serotoninergic receptors in the anteroventral preoptic region on hypoxia-induced hypothermia

Abstract

Hypoxia causes a regulated decrease in body temperature (Tb). There is circumstantial evidence that the neurotransmitter serotonin (5-HT) in the anteroventral preoptic region (AVPO) mediates this response. However, which 5-HT receptor(s) is (are) involved in this response has not been assessed. Thus, we investigated the participation of the 5-HT receptors (5-HT 1, 5-HT 2, and 5-HT 7) in the AVPO in hypoxic hypothermia. To this end, Tb of conscious Wistar rats was monitored by biotelemetry before and after intra-AVPO microinjection of methysergide (a 5-HT 1 and 5-HT 2 receptor antagonist, 0.2 and 2 μg/100 nL), WAY-100635 (a 5-HT 1A receptor antagonist, 0.3 and 3 μg/100 nL), and SB-269970 (a 5-HT 7 receptor antagonist, 0.4 and 4 μ/100 nL), followed by 60 min of hypoxia exposure (7% O 2). During the experiments, the mean chamber temperature was 24.6 ± 0.7 °C (mean ± SE) and the mean room temperature was 23.5 ± 0.8 °C (mean ± SE). Intra-AVPO microinjection of vehicle or 5-HT antagonists did not change Tb during normoxic conditions. Exposure of rats to 7% of inspired oxygen evoked typical hypoxia-induced hypothermia after vehicle microinjection, which was not affected by both doses of methysergide. However, WAY-100635 and SB-269970 treatment attenuated the drop in Tb in response to hypoxia. The effect was more pronounced with the 5-HT 7 antagonist since both doses (0.4 and 4 μg/0.1μL) were capable of attenuating the hypothermic response. As to the 5-HT 1A antagonist, the attenuation of hypoxia-induced hypothermia was only observed at the higher dose. Therefore, the present results are consistent with the notion that 5-HT acts on both 5-HT 1A and 5-HT 7 receptors in the AVPO to induce hypothermia, during hypoxia.