Lateral habenula cannabinoid CB1 receptor involvement in drug-associated impulsive behavior.
Animal and human studies show that cannabis or its derivatives can increase relapse to cocaine seeking following withdrawal. Moreover, cannabis use in humans is associated with impulse control deficits and animal studies implicate endogenous cannabinoids (eCB) in several impulsivity constructs. However, the brain areas where cannabinoids might control impulsivity or cocaine seeking are largely unknown. Here, we assess Lateral Habenula (LHb) involvement on performance in the 5-choice serial reaction time task (5CSRTT) in rats and investigate whether LHb cannabinoid CB1 receptors (CB1R) are involved in these effects. Systemic cocaine increased premature responding, a measure of impulsivity, at a dose (5 mgkg) that did not alter other measures of task performance. Intra-LHb infusion of the CB1R antagonist AM251 blocked this effect. Systemic injection of the psychoactive constituent of cannabis, Δ