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

Porras G(1), Di Matteo V, Fracasso C, Lucas G, De Deurwaerdère P, Caccia S, Esposito E, Spampinato U.

Author information:
(1)Laboratoire de Neuropsychobiologie des Désadaptations, UMR CNRS
5541-Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, Boîte Postale
31, 33076 Bordeaux Cedex, France.

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.

 

Auteurs Bordeaux Neurocampus