Involvement of CB1 cannabinoid receptors in cocaine‐induced locomotor sensitization after single pre‐exposure in mice

Abstract

Repeated psychostimulant exposure produces behavioral sensitization resulting from synaptic plasticity which may play a role in addiction. It has been suggested a role for the endocannabinoid system in synaptic plasticity, but little is known about its role in psychostimulant‐induced behavioral effects. We examined the involvement of CB1 cannabinoid receptors, using SR141716A (SR) a selective CB1 antagonist, on cocaine‐induced locomotor activity in Swiss Webster mice exposed 24 hr prior to saline or cocaine (20 mg/kg). Mice were tested in chambers equipped with motion‐sensitive detectors. A single cocaine injection 24 hr before the test produced increases in cocaine effects on locomotor activity, compared to saline 24 hr prior. SR (0.3–3.0 mg/kg i.p.) 40 min before cocaine dose‐dependently blocked the pretreatment effect of cocaine. A trend toward significance was also found when SR 1 mg/kg was administered in naïve mice 40 min before 10 or 20 mg/kg cocaine. The results suggest that endogenous cannabinoids released by cocaine might play a role in the development of behavioral sensitization induced by single cocaine pre‐exposure in mice. Since behavioral sensitization might play a role in the long‐term behavioral effects of cocaine, this study provides further evidence that the cannabinoid system could be an important target in the search for medications to treat cocaine abuse. Supported by NIDA/NIH/DHHS

Cocaine-induced endocannabinoid release modulates behavioral and neurochemical sensitization in mice

“…(0.1 ml/10 g), and the respective vehicles served as control injections. Drug doses and pre‐treatment times are from a preliminary study presented in abstract form (Tronci & Tanda ).…”