A small number of studies have examined the effects of 5-HT2C receptor ligands on ethanol maintained behavior. In rats trained to discriminate ethanol from saline, mCPP produced ethanol-appropriate responding. However, the fact that this effect was blocked by a selective 5-HT1B receptor antagonist, GR 127935, as well as the 5-HT2B/2C receptor antagonist SB 206553 makes it difficult to draw definitive conclusions about the role of 5-HT2C receptors in this response (Maurel et al. 1998). Meta-chlorophenylpiperazine also reduced operant responding for ethanol, but since no antagonist studies were performed, the contribution of 5-HT2C receptors to this response is not clear (Maurel et al. 1999a). Likewise, although a high dose of mCPP reduced ethanol drinking, it is also not clear to what extent this response involves 5-HT2C receptor stimulation (Maurel et al. 1999b).
Fenfluramine reduced operant responding for ethanol, and this effect was reversed by SB 242084 suggesting a primary role for 5-HT2C receptors in the action of fenfluramine (Tomkins et al. 2002). SB 242084 alone increased responding for ethanol, making it difficult to determine whether the reversal of fenfluramine's effect represents a functional rather than a pharmacological antagonism at 5-HT2C receptors. The latter possibility is supported by the finding that ethanol maintained responding was reduced by a specific 5-HT2C receptor agonist, Ro60-0175 (Tomkins et al. 2002). These bidirectional effects of Ro60-1075 and SB 242084 on responding for ethanol suggest a tonic modulation of this behavior by 5-HT2C receptor-mediated neurotransmission.
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