Δ9-THC REINSTATES BEER- AND SUCROSE-SEEKING BEHAVIOUR IN ABSTINENT RATS: COMPARISON WITH MIDAZOLAM, FOOD DEPRIVATION AND PREDATOR ODOUR

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Abstract
Aims: Recent studies suggest that cannabinoid receptor agonists may promote relapse to drug-seeking behaviour after a period of abstinence. In this study, the ability of Δ9-tetrahydrocannabinol (THC) to reinstate previously reinforced responding for alcoholic and non-alcoholic beverages was assessed in rats using a novel lick-based paradigm. Methods: Rats were initially given free access to beer (containing 4.5% ethanol v/v), near-beer (a beverage that looks and tastes like beer but contains Results: In Experiment 1, the cannabinoid receptor agonist Δ9-THC (1 mg/kg) significantly reinstated responding, previously reinforced with beer or near-beer. The effect was unlikely to be caused by increased appetite because 24 h food-deprivation had no such effect. Exposure to cat odour in the test chamber failed to reinstate responding for beer or near-beer and caused a complete inhibition of responding. In Experiment 2, Δ9-THC (0.3 and 1 but not 3 mg/kg) again reinstated beer-seeking behaviour while the 1 mg/kg dose also reinstated responding in sucrose trained animals. Midazolam (0.15 mg/kg but not 0.5 or 1.5 mg/kg) produced a modest reinstatement of beer-seeking but had no effect on sucrose-seeking behaviour. Conclusions: The finding that Δ9-THC can reinstate alcohol-seeking provides the impetus for further research into the involvement of the cannabinoid system in alcohol craving. However, the reinstatement of near-beer and sucrose-seeking behaviour caused by Δ9-THC suggests a relatively non-specific effect. This may perhaps be related to the stressor-like effects of cannabinoids, and their ability to activate key neural circuitry in the amygdala and bed nucleus of the stria terminalis.