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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 Gian Marco,
Cathala Adeline,
Neny Maud,
RougePont Françoise,
Drago Filippo,
Piazza Pier Vincenzo,
Spampinato Umberto
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06356.x
Subject(s) - chemistry , nucleus accumbens , microdialysis , dopamine , agonist , serotonin , endocrinology , medicine , 5 ht2c receptor , inverse agonist , 5 ht receptor , prefrontal cortex , receptor , neuroscience , psychology , biochemistry , cognition
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. Intra‐mPFC injection of the 5‐HT 2C R inverse agonist SB 206553 (0.5 μg/0.2 μL), 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 (0.5 μg/0.2 μL), 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 (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‐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 constitutive activity participates in this interaction.