5-HT2A and 5-HT2C/2B receptor subtypes modulate dopamine release induced in vivo by amphetamine and morphine in both the rat nucleus accumbens and striatum. |
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Authors: | Grégory Porras Vincenzo Di Matteo Claudia Fracasso Guillaume Lucas Philippe De Deurwaerdère Silvio Caccia Ennio Esposito Umberto Spampinato |
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Institution: | 1. Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA;2. Department of Psychiatry, Harvard Medical School, Boston, MA, USA;3. Schizophrenia and Bipolar Disorder Program, McLean Hospital, Belmont, MA, USA;1. Department of Mathematics, Sri Aurobindo College, University of Delhi, New Delhi, Delhi 110017, India;2. Department of Mathematics, Deshbandhu college, University of Delhi, New Delhi, Delhi 110019, India;3. Department of Commerce, Sri Aurobindo College, University of Delhi, New Delhi, Delhi 110017, India;4. Department of Physics, Deshbandhu college, University of Delhi, New Delhi, Delhi 110019, India;1. Translational Research Center, University Hospital of Psychiatry, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Bern, Switzerland;2. Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium;3. Multiversum, Boechout, Belgium;4. Department of Radiology, Antwerp University Hospital & University of Antwerp, Antwerp, Belgium;5. University Psychiatric Hospital Antwerp, Campus Duffel, Belgium |
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Abstract: | In vivo microdialysis and single-cell extracellular recordings were used to assess the involvement of serotonin(2A) (5-HT(2A)) and serotonin(2C/2B) (5-HT(2C/2B)) receptors in the effects induced by amphetamine and morphine on dopaminergic (DA) activity within the mesoaccumbal and nigrostriatal pathways. The increase in DA release induced by amphetamine (2 mg/kg i.p.) in the nucleus accumbens and striatum was significantly reduced by the selective 5-HT(2A) antagonist SR 46349B (0.5 mg/kg s.c.), but not affected by the 5-HT(2C/2B) antagonist SB 206553 (5 mg/kg i.p.). In contrast, the enhancement of accumbal and striatal DA output induced by morphine (2.5 mg/kg s.c.), while insensitive to SR 46349B, was significantly increased by SB 206553. Furthermore, morphine (0.1-10 mg/kg i.v.)-induced increase in DA neuron firing rate in both the ventral tegmental area and the substantia nigra pars compacta was unaffected by SR 46349B (0.1 mg/kg i.v.) but significantly potentiated by SB 206553 (0.1 mg/kg i.v.). These results show that 5-HT(2A) and 5-HT(2C) receptors regulate specifically the activation of midbrain DA neurons induced by amphetamine and morphine, respectively. This differential contribution may be related to the specific mechanism of action of the drug considered and to the neuronal circuitry involved in their effect on DA neurons. Furthermore, these results suggest that 5-HT(2C) receptors selectively modulate the impulse flow-dependent release of DA. |
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