Effect of co-injection of arachydonilcyclopropylamide and ethanol on conditioned place preference in rats

A combination of cannabis with even a small amount of ethanol can alter the brain function, more than either drug alone. To investigate the interacting effects of the co-administration of a low dose of ethanol and a cannabinoid CB1 receptor agonist, arachidonylcyclopropylamide (ACPA) on the conditioned place preference (CPP) test in male Wistar rats, ACPA was injected into the ventral tegmental area (VTA), basolateral amygdala (BLA) or ventral hippocampus (VH) in combination with ethanol during the conditioning or testing phase. Using a 3-day schedule of conditioning, low doses of ethanol (0.25, 0.5 and 1 g/kg, i.p.) did not induce CPP or conditioned place aversion (CPA). In the second experiment, bilateral intra-VTA injection of the cannabinoid CB1 receptor agonist, arachidonylcyclopropylamide (ACPA; 0.5 and 1 ng/rat) alone or with ethanol (0.5 g/kg) induced a significant CPA. Bilateral intra-BLA injection of ACPA induced significant CPP, while co-administration of the same doses of ACPA with ethanol (0.5 g/kg) induced CPA. Bilateral intra-VH injection of ACPA by itself produced both CPP and CPA in a dose-dependent manner. Co-administration of an ineffective dose of ACPA (9 ng/rat, intra-VH) with ethanol also induced significant CPA. In the animals that had received ethanol during the conditioning phase, intra-VTA or -VH injection of ACPA, 5 min before the testing phase, produced CPP while intra-BLA injection of the agonist produced CPA. None of the treatments, except intra-VH injection of ACPA, had an effect on locomotor activity. In conclusion, there may be a functional interaction between endocannabinoid system and ethanol in mediating reward or aversion.

► Intra-VTA injection of ACPA alone or with ethanol induced CPA. ► Intra-BLA injection of ACPA induced CPP. ► Intra-BLA injection of ACPA plus ethanol induced CPA. ► Intra-VH injection of ACPA dose-dependently produced both CPA and CPP. ► Intra-VH injection of ACPA plus ethanol also induced CPA.