The aim of the present study was to evaluate the interaction between the CB1 cannabinoid receptors and the endogenous opioid system by assaying anxiety likebehaviour related to acetic acid-induced visceral pain in adolescent mice of both sexes lacking CB1 receptors. The elevated plus maze and acetic acid-induced writhing tests were used in order to evaluate the effect of morphine (MOR) on the anxiety like-behaviour associated to visceral pain. CB1 knockout (CB1 KO) and wild-type (WT) mice were pre-treated with MOR (3 mg/kg or 9 mg/kg i.p.) or saline (SAL) injection 20 minutes before acetic acid (1.5% i.p.) or SAL administration, and immediately after, the total number of writhes or anxiety-like responses were registered for a period of 20 min. MOR (3 mg/kg) decreased and MOR (9 mg/kg) completely blocked the nociceptive response (expressed as percentage of writhing inhibition) compared to their control groups (mice only treated with acetic acid) (p<0.001) in both sexes and genotypes. The anxiety-like behaviour (expressed as the percentage of time and entries in the open arms) increased in mice only treated with acetic acid (p<0.01), in both sexes and genotypes. In addition, MOR 9 mg/kg
attenuated the anxiogenic-like effect (expressed as the percentage of entries in the open arms) in CB1 KO male mice compared to their respective WT (p<0.05), but not in CB1 KO female mice. In conclusion, the lack of CB1 receptor could modulate the anxiety-like behaviour associated to acetic acid-induced visceral pain in male mice pre-treated with MOR but not in females. UBACyT N° 20020160100120BA, CONICET PIP N° 00269