Serotonin2C receptors modulate dopamine transmission in the nucleus accumbens independently of dopamine release: behavioral, neurochemical and molecular studies with cocaine.
Addiction Biology. 2014-03-24; 20(3): 445-457
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1. Addict Biol. 2015 May;20(3):445-57. doi: 10.1111/adb.12137. Epub 2014 Mar 24.
Serotonin2C receptors modulate dopamine transmission in the nucleus accumbens
independently of dopamine release: behavioral, neurochemical and molecular
studies with cocaine.
Cathala A(1), Devroye C, Maitre M, Piazza PV, Abrous DN, Revest JM, Spampinato U.
(1)Neurocentre Magendie, Physiopathology of Addiction Group, Inserm U862, France;
Université de Bordeaux, France.
In keeping with its ability to control the mesoaccumbens dopamine (DA) pathway,
the serotonin2C receptor (5-HT2C R) plays a key role in mediating the behavioral
and neurochemical effects of drugs of abuse. Studies assessing the influence of
5-HT2C R agonists on cocaine-induced responses have suggested that 5-HT2C Rs can
modulate mesoaccumbens DA pathway activity independently of accumbal DA release,
thereby controlling DA transmission in the nucleus accumbens (NAc). In the
present study, we assessed this hypothesis by studying the influence of the
5-HT2C R agonist Ro 60-0175 on cocaine-induced behavioral, neurochemical and
molecular responses. The i.p. administration of 1 mg/kg Ro 60-0175 inhibited
hyperlocomotion induced by cocaine (15 mg/kg, i.p.), had no effect on
cocaine-induced DA outflow in the shell, and increased it in the core subregion
of the NAc. Furthermore, Ro 60-0175 inhibited the late-onset locomotion induced
by the subcutaneous administration of the DA-D2 R agonist quinpirole (0.5 mg/kg),
as well as cocaine-induced increase in c-Fos immunoreactivity in NAc subregions.
Finally, Ro 60-0175 inhibited cocaine-induced phosphorylation of the DA and c-AMP
regulated phosphoprotein of Mr 32 kDa (DARPP-32) at threonine residues in the NAc
core, this effect being reversed by the selective 5-HT2C R antagonist SB 242084
(0.5 mg/kg, i.p.). Altogether, these findings demonstrate that 5-HT2C Rs are
capable of modulating mesoaccumbens DA pathway activity at post-synaptic level by
specifically controlling DA signaling in the NAc core subregion. In keeping with
the tight relationship between locomotor activity and NAc DA function, this
interaction could participate in the inhibitory control of cocaine-induced
© 2014 Society for the Study of Addiction.
PMID: 24661380 [Indexed for MEDLINE]