Title

 

Authors

G.M. Leggio, A. Chatala, M. Neny, F. Rouge-Pont, F. Drago, P.V. Piazza and U. Spampinato

Catania

 

Abstract

Control of the mesoaccumbens dopamine (DA) pathway by central serotonin2C receptors (5-HT2CRs) involves different 5- HT2CR populations located within multiple brain areas. Here, using in vivo microdialysis in halothane-anesthetized rats, we assessed the role of medial prefrontal cortex (mPFC) 5- HT2CRs in the control of basal and activated accumbal DA outflow, to identify the modalities of their recruitment and the role of 5-HT2CR constitutive activity. Intra-mPFC injection of the 5-HT2CR inverse agonist SB 206553 (0.5 lg/0.2 lL), without effect by itself, decreased accumbal DA outflow induced by morphine (2.5–10 mg/kg, s.c.), haloperidol (0.01 mg/kg, s.c.) or GBR 12909 (2.5 mg/kg, i.p.). Conversely, intra-mPFC injection of the 5-HT2CR antagonist SB 242084 (0.5 lg/0.2 lL), without effect by itself, decreased the effect of 10 mg/kg morphine, the only drug enhancing basal 5- HT outflow in the mPFC. The inhibitory effect of SB 206553 on 2.5 mg/kg morphine-stimulated DA outflow was suppressed by the concomitant intra-mPFC injection of SB 242084. Finally, changes of basal DA outflow induced by the 5-HT2CR agonist Ro 60-0175 (3 mg/kg, i.p.) or SB 206553 (5 mg/kg, i.p.) were unaffected by intra-mPFC injection of SB 242084. These results, showing that 5-HT2CR antagonist and inverse agonist behave differently in vivo, demonstrate that mPFC 5-HT2CRs facilitate activated accumbal DA outflow and that 5-HT2CR constitutive activity participates in this interaction.