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Effects of rimonabant on the development of single dose-induced behavioral sensitization to ethanol, morphine and cocaine in mice.

Abstract：

RATIONALE:The endocannabinoid system has been implicated in the neurobiological mechanism underlying drug addiction, especially the primary rewarding dopamine-dependent processes. Therefore, endocannabinoid receptor antagonists, such as the CB1 cannabinoid antagonist rimonabant, have been proposed as candidates for preventive addiction therapies. OBJECTIVES:Investigate the possible involvement of CB1 receptors in the development of behavioral sensitization to ethanol, morphine and cocaine in mice. METHODS:We compared the effects of different doses of rimonabant (0.3, 1, 3 and 10mg/kg) on spontaneous locomotor activity in the open-field, hyperlocomotion induced by acute administration of ethanol (1.8g/kg), morphine (20mg/kg) or cocaine (10mg/kg) and on subsequent drug-induced locomotor sensitization using a two-injection protocol in mice. We also investigated a possible depressive-like effect of an acute rimonabant challenge at the highest dose and its potential anxiogenic property. RESULTS:At the highest dose, rimonabant abolished ethanol- and cocaine-induced hyperlocomotion and behavioral sensitization without modifying spontaneous and central locomotor activity or inducing depressive-like behavior on the forced swim test in mice. The other doses of rimonabant also selectively blocked acute ethanol-induced central hyperlocomotion. Although rimonabant at 0.3 and 1mg/kg potentiated the central hyperlocomotion induced by acute morphine injection, it was effective in attenuating morphine-induced behavioral sensitization at all doses. CONCLUSIONS:Because the neural basis of behavioral sensitization has been proposed to correspond to some components of addiction, our findings indicate that the endocannabinoid system might be involved in ethanol, cocaine and morphine abuse.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Marinho EA,Oliveira-Lima AJ,Santos R,Hollais AW,Baldaia MA,Wuo-Silva R,Yokoyama TS,Takatsu-Coleman AL,Patti CL,Longo BM,Berro LF,Frussa-Filho R

doi

10.1016/j.pnpbp.2014.11.010

subject

Has Abstract

pub_date

2015-04-03 00:00:00

pages

22-31

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(14)00236-X

journal_volume

pub_type

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Effects of rimonabant on the development of single dose-induced behavioral sensitization to ethanol, morphine and cocaine in mice.