Region‐dependent regulation of mesoaccumbens dopamine neuronsin vivoby the constitutive activity of central serotonin2C receptors

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Abstract
Central serotonin2C receptors (5‐HT2CRs) control the mesoaccumbens dopamine (DA) pathway. This control involves the constitutive activity (CA) of 5‐HT2CRs, and is thought to engage regionally distinct populations of 5‐HT2CRs, leading to opposite functional effects. Here, usingin vivomicrodialysis in halothane‐anesthetized rats, we investigated the relative contribution of ventral tegmental area (VTA) and nucleus accumbens shell (NAc) 5‐HT2CRs in the phasic/tonic control of accumbal DA release, to specifically identify the nature (inhibition/excitation) of the control, and the role of the 5‐HT2CR CA. Intra‐VTA injections of the selective 5‐HT2CR antagonists SB 242084 and/or SB 243213 (0.1–0.5 µg/0.2 µL) prevented the decrease in accumbal DA outflow induced by the 5‐HT2CR agonist Ro 60–0175 (3 mg/kg, i.p), but did not affect the increase in DA outflow induced by the 5‐HT2CR inverse agonist SB 206553 (5 mg/kg, i.p). Intra‐NAc infusions of SB 242084 (0.1–1 µm) blocked Ro 60–0175‐ and SB 206553‐induced changes of DA outflow. Intra‐NAc, but not intra‐VTA administration of SB 206553 increased basal DA outflow. These findings demonstrate that both VTA and NAc 5‐HT2CRs participate in the inhibitory control exerted by 5‐HT2CRs on accumbal DA release, and that the NAc shell may represent a primary action site for the CA of 5‐HT2CRs.