Asenapine induces differential regional effects on serotonin receptor subtypes

作者：Tarazi F I^*; Moran Gates T; Wong E H F; Henry B; Shahid M

来源：Journal of Psychopharmacology, 2010, 24(3): 341-348.

DOI：10.1177/0269881108095704

• asenapine
• caudate putamen
• frontal cortex
• hippocampus
• serotonin receptor

Asenapine, a novel psychopharmacologic agent being developed for the treatment of schizophrenia and bipolar disorder, has high affinity for a wide range of receptors, including the serotonergic receptors 5-HT(1A), 5-HT(1B), 5-HT(2A), 5-HT(2B), 5-HT(2C), 5-HT(5A), 5-HT(6) and 5-HT(7). We examined the long-term effects in rat brain of multiple doses of asenapine on representative serotonin receptor subtypes: 5-HT(1A), 5-HT(2A) and 5-HT(2C). Rats were given asenapine (0.03, 0.1 or 0.3 mg/kg) subcutaneously twice daily or vehicle for 4 weeks. Brain sections were collected from the medial prefrontal cortex (mPFC), dorsolateral frontal cortex (DFC), caudate putamen, nucleus accumbens, hippocampal CA(1) and CA(3) regions, and entorhinal cortex and processed for in-vitro receptor autoradiography. Asenapine 0.1 and 0.3 mg/kg significantly increased 5-HT(1)A binding in mPFC (by 24% and 33%, respectively), DFC (27%, 31%) and hippocampal C(A1) region (23%, 25%) (all P < 0.05). All three asenapine doses (0.03, 0.1 and 0.3 mg/ kg) significantly decreased 5-HT(2A) binding by a similar degree in mPFC (40%, 44%, 47%, respectively) and DFC (45%, 51%, 52%) (all P < 0.05), but did not alter 5-HT(2A) binding in the other brain regions studied. In contrast to the effects on 5-HT(1A) and 5-HT(2A) receptors, asenapine did not alter 5-HT(2C) binding in any brain region examined at the doses tested. Our results indicate that repeated administration of asenapine produces regional-specific effects on 5-HT(1A) and 5-HT(2A) receptors in rat forebrain regions, which may contribute to the distinctive psychopharmacologic profile of asenapine.

• 出版日期2010-3