The cannabinoid CB1 receptor system modulates behavioral phenomena predictive of relapse during extinction of self‐administration in mice

Abstract

The endogenous cannabinoid system plays a defined role in the extinction of fear conditioning and spatial memory. It is also well‐established that manipulation of CB1 receptors modulates positively‐reinforced behaviors such as drug self‐administration in laboratory animals, but whether and how the CB1 system regulates extinction of such behaviors is poorly understood. We investigated whether the CB1 receptor antagonist SR141716 affects several extinction behaviors and/or the rate of extinction learning in mice trained to self‐administer palatable food (32% corn oil or 50% Ensure p.o.) or cocaine (0.3 mg/kg/inf i.v.). Following stable self‐administration behavior, mice were pretreated prior to daily extinction sessions with 3.0 mg/kg SR141716 or vehicle, and effects on initial extinction burst responding, spontaneous recovery, CS‐ or prime‐induced reinstatement, and daily extinction rates were assessed. SR141716 pretreatment attenuated initial burst responding, spontaneous recovery, and CS‐ and prime‐ induced reinstatement, and SR141716‐treated mice also required fewer trials to reach daily extinction criterion than vehicle‐treated mice. 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 relapse behaviors during extinction and enhance extinction learning.