Differential effect of opioid and cannabinoid receptor blockade on heroin-seeking reinstatement and cannabinoid substitution in heroin-abstinent rats.
Summary of "Differential effect of opioid and cannabinoid receptor blockade on heroin-seeking reinstatement and cannabinoid substitution in heroin-abstinent rats."
Background and purpose: Opioids and cannabinoids strictly interact in drug addiction and relapse. We investigated the effect of the opioid receptor antagonist naloxone and/or the cannabinoid CB1 receptor antagonist rimonabant on cannabinoid-induced reinstatement of heroin-seeking and on cannabinoid substitution in heroin-abstinent rats. Experimental approach: Rats were trained to self-administer heroin (30µg·kg(-1) per infusion) under an FR1 reinforcement schedule. After extinction of self-administration (SA) behaviour, we verified the effect of naloxone (0.1-1mg·kg(-1) ) and rimonabant (0.3-3mg·kg(-1) ) on the reinstatement of heroin-seeking induced by primings with the CB1 receptor agonist WIN55,212-2 (WIN, 0.15-0.3mg·kg(-1) ). Then, in a parallel set of heroin-trained rats, we evaluated whether WIN (12.5 µg·kg(-1) per infusion) SA substituted for heroin SA after different periods of extinction. In groups of rats in which substitution occurred, we studied the effect of both antagonists on cannabinoid intake. Key results: Cannabinoid-induced reinstatement of heroin-seeking was significantly attenuated by naloxone (1mg·kg(-1) ) and rimonabant (3mg·kg(-1) ) and fully blocked by co-administration of sub-threshold doses of the two antagonists. Moreover, contrary to immediate (1 day) or delayed (90 days) drug substitution, rats readily self-administered WIN when access was given after 7, 14 or 21 days of extinction from heroin, and showed a response rate that was positively correlated with the extinction period. In these animals, cannabinoid intake was increased by naloxone (1mg·kg(-1) ) and decreased by rimonabant (3mg·kg(-1) ). Conclusions and implications: Our findings extend previous research on the cross-talk between cannabinoid and opioid receptors in relapse mechanisms, which suggests a differential role in heroin-seeking reinstatement and cannabinoid substitution in heroin-abstinent rats.
Affiliation
Institute of Neuroscience-Cagliari, CNR National Research Council of Italy, Centre of Excellence "Neurobiology of Dependence" and Department of Neuroscience, University of Cagliari, Cittadella Universitaria di Monserrato, Italy.
Journal Details
This article was published in the following journal.
Name: British journal of pharmacology
ISSN: 1476-5381
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21518339
- DOI: http://dx.doi.org/10.1111/j.1476-5381.2011.01459.x
Medical and Biotech [MESH] Definitions
Receptor, Cannabinoid, Cb2
A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.
Receptor, Cannabinoid, Cb1
A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.
Enkephalin, D-penicillamine (2,5)-
A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity.
Heroin Dependence
Strong dependence, both physiological and emotional, upon heroin.
Angiopoietin-2
An angiopoietin that is closely related to ANGIOPOIETIN-1. It binds to the TIE-2 RECEPTOR without receptor stimulation and antagonizes the effect of ANGIOPOIETIN-1. However its antagonistic effect may be limited to cell receptors that occur within the vasculature. Angiopoietin-2 may therefore play a role in down-regulation of BLOOD VESSEL branching and sprouting.
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