Serotonin2C receptor stimulation inhibits cocaine-induced Fos expression and DARPP-32 phosphorylation in the rat striatum independently of dopamine outflow.
Neuropharmacology. 2015-02-01; 89: 375-381
DOI: 10.1016/j.neuropharm.2014.10.016
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1. Neuropharmacology. 2015 Feb;89:375-81.
Serotonin2C receptor stimulation inhibits cocaine-induced Fos expression and
DARPP-32 phosphorylation in the rat striatum independently of dopamine outflow.
Devroye C(1), Cathala A, Maitre M, Piazza PV, Abrous DN, Revest JM, Spampinato U.
Author information:
(1)Inserm, U862, Neurocentre Magendie, Physiopathology of Addiction Group,
Bordeaux F-33000, France.
The serotonin(2C) receptor (5-HT(2C)R) is known to control dopamine (DA) neuron
function by modulating DA neuronal firing and DA exocytosis at terminals. Recent
studies assessing the influence of 5-HT(2C)Rs on cocaine-induced neurochemical
and behavioral responses have shown that 5-HT2CRs can also modulate mesoaccumbens
DA pathway activity at post-synaptic level, by controlling DA transmission in the
nucleus accumbens (NAc), independently of DA release itself. A similar mechanism
has been proposed to occur at the level of the nigrostriatal DA system. Here,
using in vivo microdialysis in freely moving rats and molecular approaches, we
assessed this hypothesis by studying the influence of the 5-HT(2C)R agonist Ro
60-0175 on cocaine-induced responses in the striatum. The intraperitoneal (i.p.)
administration of 1 mg/kg Ro 60-0175 had no effect on the increase in striatal DA
outflow induced by cocaine (15 mg/kg, i.p.). Conversely, Ro 60-0175 inhibited
cocaine-induced Fos immunoreactivity and phosphorylation of the DA and c-AMP
regulated phosphoprotein of Mr 32 kDa (DARPP-32) at threonine 75 residue in the
striatum. Finally, the suppressant effect of Ro 60-0175 on cocaine-induced
DARPP-32 phosphorylation was reversed by the selective 5-HT(2C)R antagonist SB
242084 (0.5 mg/kg, i.p.). In keeping with the key role of DARPP-32 in DA
neurotransmission, our results demonstrate that 5-HT(2C)Rs are capable of
modulating nigrostriatal DA pathway activity at post-synaptic level, by
specifically controlling DA signaling in the striatum.
DOI: 10.1016/j.neuropharm.2014.10.016
PMID: 25446572 [Indexed for MEDLINE]