| Title | In vivo evidence that constitutive activity of serotonin(2C) receptors in the medial prefrontal cortex participates in the control of dopamine release in the rat nucleus accumbens: differential effects of inverse agonist versus antagonist. | | Author(s) | Leggio GM, Cathala A, Neny M, Rouge-Pont F, Drago F, Piazza PV, Spampinato U | | Institution | Inserm, U862, Neurocentre Magendie, Physiopathology of Addiction group, Bordeaux, F-33000, France. | | Source | J Neurochem 2009 Aug 22. | | Abstract | Abstract Control of the mesoaccumbens dopamine (DA) pathway by central serotonin(2C) receptors (5-HT(2C)Rs) involves different 5-HT(2C)R 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-HT(2C)Rs in the control of basal and activated accumbal DA outflow, to identify the modalities of their recruitment and the role of 5-HT(2C)R constitutive activity (CA). Intra-mPFC injection of the 5-HT(2C)R inverse agonist SB 206553 (0.5mug/0.2mul), 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-HT(2C)R antagonist SB 242084 (0.5mug/0.2mul), 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-HT(2C)R agonist Ro 60-0175 (3mg/kg, i.p.) or SB 206553 (5mg/kg, i.p.) were unaffected by intra-mPFC injection of SB 242084. These results, showing that 5-HT(2C)R antagonist and inverse agonist behave differently in vivo, demonstrate that mPFC 5-HT(2C)Rs facilitate activated accumbal DA outflow and that 5-HT(2C)R CA participates in this interaction. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19702657 |
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