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Modulation of stress- and cocaine prime-induced reinstatement of conditioned place preference after memory extinction through dopamine D3 receptor.

Abstract：

:Accumulating evidence indicates that dopamine (DA) D3 receptor (DAD3R) antagonists appear highly promising in attenuating cocaine reward and relapse in preclinical models of addiction. In the present study, we investigated the effects of the selective DAD3R antagonist SB-277011-A on the reinstatement of cocaine-induced conditioned place preference (CPP) produced by a priming dose of cocaine, by social defeat stress and by two kinds of physiological stressors (restraint and tail pinch) in male adult mice. We also explored reinstatement-related plasma corticosterone levels (as marker of stress response) and the effects of blocking DAD3R. Administration of SB-277011-A (24 or 48 mg/kg i.p.) did not modify conditioned reinstatement of cocaine seeking triggered by cocaine prime. By contrast, we found that the vulnerability to reinstatement of the CPP of defeated animals that have undergone CPP extinction was abolished by the DAD3R antagonist (24 mg/kg) given 30 min before the test session. Reactivation of the CPP response produced by physiological stress stimuli was also attenuated by SB-277011-A (48 mg/kg i.p.). On the other hand, the blockade of DAD3R significantly prevented the increased corticosterone release during reinstatement of cocaine-induced CPP that was seen in social defeated animals, in mice suffering physiological stress and after cocaine prime. Present results demonstrate a modulation by DAD3R of the reactivation of the incentive value of cocaine-associated cues induced by social and physiological stress stimuli, which was associated to a glucocorticoid-dependent mechanism. Our results also point to a possible potential therapeutic use of selective DAD3R antagonists for the prevention of stress-induced cocaine-seeking and relapse.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Guerrero-Bautista R,Do Couto BR,Hidalgo JM,Cárceles-Moreno FJ,Molina G,Laorden ML,Núñez C,Milanés MV

doi

10.1016/j.pnpbp.2019.01.017

subject

Has Abstract

pub_date

2019-06-08 00:00:00

pages

308-320

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(18)30571-2

journal_volume

pub_type

杂志文章

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Modulation of stress- and cocaine prime-induced reinstatement of conditioned place preference after memory extinction through dopamine D3 receptor.