Cannabinoid CB₁ receptors mediate the effects of corticotropin‐releasing factor on the reinstatement of cocaine seeking and expression of cocaine‐induced behavioural sensitization

Abstract

BACKGROUND AND PURPOSEThe endocannabinoid and corticotropin-releasing factor (CRF) systems have been implicated in several long-lasting behavioural effects of prior cocaine experience. The present experiments were designed to probe functional interactions between endocannabinoids and CRF by testing the role of cannabinoid CB1 receptors in cocaine-related behaviours induced or mediated by CRF. EXPERIMENTAL APPROACHIn Experiment 1, rats trained to self-administer cocaine were pretreated with the CB1 receptor antagonist, AM251 (0, 10, 100 or 200 mg, i.c.v.), before tests for reinstatement in response to CRF (0, 0.5 mg, i.c.v.), intermittent footshock stress (0, 0.9 mA) or cocaine (0, 10 mg·kg -1 , i.p.). In Experiment 2, rats pre-exposed to cocaine (15-30 mg·kg KEY RESULTSPretreatment with AM251 selectively interfered with CRF-, but not footshock-or cocaine-induced reinstatement. AM251 blocked the expression of behavioural sensitization induced by challenge injections of both CRF and cocaine. CONCLUSIONS AND IMPLICATIONSThese findings reveal a mediating role for CB1 receptor transmission in the effects of CRF on cocaine-related behaviours. Abbreviations2-AG, 2-arachidonoylglycerol; BLA, basolateral amygdala; BNST, bed nucleus of the stria terminalis; CeA, central nucleus of the amygdala; CPP, conditioned place preference;

Neurobiological Interactions Between Stress and the Endocannabinoid System

“…Without further evidence to help resolve this discrepancy, one interpretation could be that eCB signaling contributes to stress-induced alcohol consumption but not stress-induced relapse following cessation. Similar discrepancies have been found with cocaine whereby CB1 receptor antagonism does not block footshock-induced reinstatement of cocaine-seeking behavior (De Vries et al, 2001;Kupferschmidt et al, 2012) but has been found to reverse the reinstatement of cocaine-seeking behavior in response to swim stress (Vaughn et al, 2012) or direct administration of CRH (Kupferschmidt et al, 2012). Here it is possible that the stress modality itself could have differential effects on eCB signaling (as discussed above) in which eCB signaling could be important for some forms of stress-induced cocaine reinstatement, while it is dispensable for others.…”

Effects of acute or chronic environmental enrichment on regional Fos protein expression following sucrose cue-reactivity testing in rats

“…In the present study we did not find a difference in plasma corticosterone levels between the five treatment groups. Average plasma levels were 119.0 ± 5.9 ng/mL, a value above what has been reported for non-stressed Long-Evans male rats in some (Konkle et al 2010) but not other (Kupferschmidt et al 2012) studies. For example, corticosterone levels in Long-Evans rats prior to a stress challenge but just following a behavioral test were approximately 350 ng/mL (Kupferschmidt et al).…”

Corticotropin releasing factor: A key role in the neurobiology of addiction

“…The results agree with other evidence that activation of extrahypothalamic CRF sites subserves stress-induced reinstatement behavior (Shaham et al, 1997;Erb et al, 1998;Wang et al, 2005;Wang et al, 2006;Blacktop et al, 2011). Consistent with this hypothesis, intra-VTA (Wang et al, 2005) or intracerebroventricular (Blacktop et al, 2011;Kupferschmidt et al, 2011;Brown et al, 2012;Buffalari et al, 2012;Kupferschmidt et al, 2012) infusion of CRF can reinstate cocaine-seeking behavior in rats.…”