&NA; The central serotonin2B receptor (5‐HT2BR) is a well‐established modulator of dopamine (DA) neuron activity in the rodent brain. Recent studies in rats have shown that the effect of 5‐HT2BR… Click to show full abstract
&NA; The central serotonin2B receptor (5‐HT2BR) is a well‐established modulator of dopamine (DA) neuron activity in the rodent brain. Recent studies in rats have shown that the effect of 5‐HT2BR antagonists on accumbal and medial prefrontal cortex (mPFC) DA outflow results from a primary action in the dorsal raphe nucleus (DRN), where they activate 5‐HT neurons innervating the mPFC. Although the mechanisms underlying this interaction remain largely unknown, data in the literature suggest the involvement of DRN GABAergic interneurons in the control of 5‐HT activity. The present study examined this hypothesis using in vivo (intracerebral microdialysis) and in vitro (immunohistochemistry coupled to reverse transcription‐polymerase chain reaction) experimental approaches in rats. Intraperitoneal (0.16 mg/kg) or intra‐DRN (1 &mgr;M) administration of the selective 5‐HT2BR antagonist RS 127445 increased 5‐HT outflow in both the DRN and the mPFC, these effects being prevented by the intra‐DRN perfusion of the GABAA antagonist bicuculline (100 &mgr;M), as well as by the subcutaneous (0.16 mg/kg) or the intra‐DRN (0.1 &mgr;M) administration of the selective 5‐HT1AR antagonist WAY 100635. The increase in DRN 5‐HT outflow induced by the intra‐DRN administration of the selective 5‐HT reuptake inhibitor citalopram (0.1 &mgr;M) was potentiated by the intra‐DRN administration (0.5 &mgr;M) of RS 127445 only in the absence of bicuculline perfusion. Finally, in vitro experiments revealed the presence of the 5‐HT2BR mRNA on DRN GABAergic interneurons. Altogether, these results show that, in the rat DRN, 5‐HT2BRs are located on GABAergic interneurons, and exert a tonic inhibitory control on 5‐HT neurons innervating the mPFC.
               
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