5-Hydroxytryptamine inhibits neuronal high-voltage-activated calcium currents in the preoptic anterior hypothalamus via 5-hydroxytryptamine 1A and 7 receptors

5-Hydroxytryptamine (5-HT) is involved in mammalian thermoregulation of the preoptic anterior hypothalamus (PO/AH), but the underlying molecular mechanisms are not fully understood. In this study, we investigated the influence of 5-HT and agonists and antagonists of the 5-HT1A, 5-HT2A, 5-HT3 and 5-HT7 receptors on voltage-gated calcium currents in the PO/AH slice with the whole-cell patch clamp technique. The results showed that 5-HT decreased high-voltage-activated (HVA) calcium currents in PO/AH neurons in a concentration-dependent manner, but it did not affect low-voltage-activated (LVA) calcium currents. The 5-HT-induced decrease in HVA calcium currents in PO/AH neurons was facilitated by both the 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT) and the 5-HT7 receptor agonist (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin (AS 19), whereas it was inhibited by both the 5-HT1A antagonist N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl}-N-2-pyridinylcyclohexane-carboxamide (WAY 100635) and the 5-HT7 receptor antagonist 3-methylN-[(1R)-1-methyl-3-(4-methyl-1-piperidinyl)propyl]-N-methylbenzenesulfonamide hydrochloride (SB 258719). Conversely, administration of agonists and antagonists of 5-HT2A and 5-HT3 receptors did not significantly influence HVA calcium currents in PO/AH neurons. In conclusion, our findings suggested that 5-HT1A and 5-HT7 receptors were involved in the 5-HT-induced decrease of HVA calcium currents in PO/AH neurons and might contribute to the hypothermic effects of thermoregulation.