Locomotor effects of morphine or alcohol in mice after a repeated treatment with the cannabinoid agonist HU 210

Abstract The consequences of the consumption of cannabinoids with other drugs of abuse are of particular medical relevance. Several studies investigated the ability of cannabinoids to induce a locomotor cross-sensitization to other addictive drugs, but results remain inconsistent. Therefore, we investigated in mice the consequences of a repeated treatment with the cannabinoid agonist HU 210 on motor effects of morphine or alcohol. In mice receiving a daily injection of HU 210 (12.5 to 200 μg/kg) during 7 days, no hetero-sensitization to the stimulation induced by either morphine (7.5 mg/kg) or alcohol (1 or 1.5 g/kg) emerged, from 1 day up to 35 days after the end of the sub-chronic treatment with HU 210. Even a chronic treatment with a high dose of HU 210 (14 days, 200 μg/kg) induced no subsequent enhancement of the stimulant effects of morphine or alcohol. In fact, the motor stimulant effect of morphine or alcohol in chronically HU 210 pre-treated mice was even abolished until the 3rd day of abstinence. This reduction was presumably due to residual HU 210 since this effect was prevented by the cannabinoid antagonist rimonabant. Afterwards, chronically cannabinoid pre-treated mice remained less active than vehicle pre-treated mice from the 7th day up to the 35th day after the end of the 14-day treatment with HU 210. In conclusion, we failed to detect any hetero-sensitization whatever the pre-treatment regimen. However, only after the 14-day regimen, HU 210 pre-treated mice displayed a long-lasting decrease in activity, suggesting that some neuronal adaptive changes may have occurred.