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The CB1 antagonist rimonabant (SR141716) blocks cue-induced reinstatement of cocaine seeking and other context and extinction phenomena predictive of relapse.

Abstract：

:Cannabinoid CB1 antagonists decrease self-administration of palatable food and several abused drugs in animals and modulate extinction of conditioned fear responses. Less is known, however, about whether and how CB1 antagonists might modulate the extinction of appetitive behavior. Therefore, this study examined the effects of the CB1 receptor antagonist rimonabant (SR141716) during extinction of responding maintained either by cocaine or by palatable foods (corn oil or Ensure), as well as responding elicited by stimulus cues that had been paired with the presentation of cocaine (i.e., cue-induced reinstatement) or a prime (presentation of cocaine or food). The effect of rimonabant on high rate responding in water-deprived mice trained to self-administer water was also examined. In mice self-administering cocaine, rimonabant attenuated cue-induced reinstatement of cocaine self-administration, the initial burst of responding during cocaine extinction and responding during spontaneous recovery. In mice self-administering corn oil, rimonabant decreased responding during extinction and also attenuated responding that had been reinstated by a priming presentation of corn oil. Moreover, mice treated with rimonabant required fewer daily sessions to reach criterion for extinction of cocaine-maintained responding than vehicle treated mice. Also, rimonabant had no effect on the rate of operant responding in mice trained to respond for water under an FR5 schedule of reinforcement. Taken together, these data suggest that in addition to attenuating the primary reinforcing effects of both palatable foods and drugs of abuse, CB1 receptor antagonism can attenuate context and cue reactivity during extinction learning and potentially enhance extinction learning in this way.

journal_name

Drug Alcohol Depend

journal_title

Drug and alcohol dependence

authors

Ward SJ,Rosenberg M,Dykstra LA,Walker EA

doi

10.1016/j.drugalcdep.2009.07.002

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

248-55

issue

eissn

0376-8716

issn

1879-0046

pii

S0376-8716(09)00263-4

journal_volume

105

pub_type

杂志文章

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The CB1 antagonist rimonabant (SR141716) blocks cue-induced reinstatement of cocaine seeking and other context and extinction phenomena predictive of relapse.