OBJECTIVES: An increased behavioural response ("behavioural sensitization") to drugs of abuse occurs after repeated treatment. In the present study the possibility of cross-sensitization existence between various cannabinoid receptor ligands--CB1 agonist methanandamide, CB2 agonist JWH 015, and CB1 antagonist AM 251 with methamphetamine was explored.
METHODS: Locomotion in the open field was measured in naive mice and in those pre-treated acutely and repeatedly (for 8 days), respectively, with either vehicle or tested drugs.
RESULTS: Methamphetamine produced significant sensitization to its stimulatory effect on locomotion. Methanandamide pre-treatment elicited cross-sensitization to methamphetamine effect, whereas pre-treatment with JWH 015 did not. Combined pre-treatment with methamphetamine+AM 251 suppressed sensitization to methamphetamine.
CONCLUSIONS: These results suggest that the activity of the endocannabinoid system is involved in the neuronal circuitry underlying the development of sensitization to methamphetamine.