A behavioural model to reveal place preference to Δ9-tetrahydrocannabinol in mice

Abstract 

Rationale: The rewarding properties of Δ9- tetrahydrocannabinol (THC) are difficult to demonstrate in rodents using standard procedures. Objective: To evaluate the motivational responses of THC in the place conditioning paradigm in mice after minimizing the dysphoric effects of the first drug exposure and/or the consequences of its pharmacokinetic properties. Methods: Mice were conditioned to THC (1 or 5 mg/kg) using an unbiased procedure with an elevated number of pairings and long conditioning time. Results: A place aversion was observed with 5 mg/kg THC using a standard protocol. Similar results were obtained when the CB-1 receptor antagonist SR 141716A (1 mg/kg) was administered immediately after each THC conditioning period. However, mice receiving a priming THC injection and conditioned 24 h later showed a place preference with 1 mg/kg THC and no effect with 5 mg/kg THC. Conclusion: THC produces a clear place preference in mice by using a long period of conditioning and avoiding the possible dysphoric consequences of the first drug exposure.