Effects of the cannabinoid CB1 receptor antagonist rimonabant on distinct measures of impulsive behavior in rats

Abstract

Rationale Pathological impulsivity is a prominent feature in several psychiatric disorders, but detailed understanding of the specific neuronal processes underlying impulsive behavior is as yet lacking. Objectives As recent findings have suggested involvement of the brain cannabinoid system in impulsivity, the present study aimed at further elucidating the role of cannabinoid CB 1 receptor activation in distinct measures of impulsive behavior. Materials and methods The effects of the selective cannabinoid CB 1 receptor antagonist, rimonabant (SR141716A) and agonist WIN55,212-2 were tested in various measures of impulsive behavior, namely, inhibitory control in a fivechoice serial reaction time task (5-CSRTT), impulsive choice in a delayed reward paradigm, and response inhibition in a stop-signal paradigm. Results In the 5-CSRTT, SR141716A dose-dependently improved inhibitory control by decreasing the number of premature responses. Furthermore, SR141716A slightly improved attentional function, increased correct response latency, but did not affect other parameters. The CB 1 receptor agonist WIN55,212-2 did not change inhibitory control in the 5-CSRTT and only increased response latencies and errors of omissions. Coadministration of WIN55,212-2 prevented the effects of SR141716A on inhibitory control in the 5-CSRTT. Impulsive choice and response inhibition were not affected by SR141716A at any dose, whereas WIN55,212-2 slightly impaired response inhibition but did not change impulsive choice. Conclusions The present data suggest that particularly the endocannabinoid system seems involved in some measures of impulsivity and provides further evidence for the existence of distinct forms of impulsivity that can be pharmacologically dissociated.

Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats

“…26 Rimonabant also did not affect choice in a task involving delay costs, and when considered with the current data, it appears endocannabinoid signalling does not tonically regulate decision-making. 9,24 URB 597 -an FAAH inhibitor -and the synthetic CB 1 agonist WIN also did not affect choice, even though the latter drug had robust effects on trials completed and omission rates. These results seem difficult to reconcile with THC's choice effects, given all of these agents increase ligand binding at the CB 1 receptor.…”

“…Similarly, cannabinoid receptor activation, via THC or WIN, did not disrupt attention on the 5-choice serial reaction time task, which differs from the rCET only in its lack of LR/HR options. 9,24 However, when THC was administered to a subset of animals in the THC/ CBD coadministration experiment, accuracy for HR trials was impaired at a dose that previously had no effect. Indeed, an analysis of HR trials from the original THC challenge revealed a trending decline in accuracy among animals included in the coadministration experiment (Appendix 1).…”

“…[28][29][30] We are not the first group to show effects on decision-making following THC that are not replicated by a synthetic CB 1 agonist: THC, but not WIN, increased HR choice in a task involving delay costs. 9,24 Perhaps the most parsimonious explanation for the discrepancy between the effects of these agonists relates to their ability to recruit differential signalling cascades. While THC is a potent recruiter of the arrestin2 pathway, WIN and endogenous anandamide appear to signal through the more classical G-protein Gα i/o and Gβ γ pathways.…”

Impulsive Behavior and Nicotinic Acetylcholine Receptors

“…Moreover, SR141716A could prevent nicotine-induced dopamine release in the rat nucleus accumbens (67). Moreover, SR141716A has been shown to suppress impulsive behavior in rats (68).…”

Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making

“…Previous work has shown that the effects of cannabinoids on impulsive decision making have been complex and controversial. Some studies demonstrated increased impulsive choice (Hernandez et al 2014;Loflin et al 2014) while others showed unaffected or decreased impulsive choice following cannabinoid administration (McDonald et al 2003;Pattij et al 2007;Wiskerke et al 2011). It has also been suggested that genetic factors influence the effects of cannabinoids on impulsive decision making (Boomhower et al 2013) and polymorphisms in CB1R gene is involved in differential trait impulsivity (Ehlers et al 2007).…”