Contribution of CB1Rs in anxiety-related behaviors but not locomotor deficits induced by methamphetamine.

Several lines of evidence have indicated that Methamphetamine (METH) exposure leads to neurodegenerative changes in the dopaminergic neurons and subsequently may predispose users to motor deficit. On the other hand, there is a reciprocal regulation between the endocannabinoid and the dopaminergic systems. Previous studies also showed that the endocannabinoids are involved in the signaling mechanisms of various brain regions related to motor and cognitive functions. The cerebellum seems as a rational target to investigate the action of cannabinoids on motor coordination because of the high concentration of the cannabinoid receptor in the molecular layer of it and other regions involved in motor activity. The behavioral effects of systemic CBR agonist (3mg/kg/day WIN55,212-2) and antagonist (10mg/kg SR141716A) treatment on METH-induced motor deficits in rats were assessed using open field, rota-rod, and grip tests. Our results show that motor coordination and muscle strength significantly decreased in the animals received METH (5mg/kg, daily×3days) as compared to the saline groups. Pretreatment with neither WIN55,212-2 nor SR141716A had no effects on impairments induced by METH. Meanwhile motor activity and anxiety-related behaviors significantly increased in the animals that received METH and pretreatment with SR141716A significantly attenuated anxiety-related behaviors induced by METH. In sum, our findings show that anxiety-related behaviors induced by METH can be affected by CB1R manipulations and provide evidence that antagonism of CB1R at high dose cannot reverse the deteriorative METH-induced locomotion changes.