Cannabidiol reverses the mCPP‐induced increase in marble‐burying behavior

Cannabidiol (CBD), one of the main components of Cannabis sp., presents clinical and preclinical anxiolytic properties. Recent results using the marble‐burying test (MBT) suggest that CBD can also induce anticompulsive‐like effects. Meta‐chloro‐phenyl‐piperazine (mCPP) is a nonspecific serotonergic agonist (acting mainly at 5HT1A, 5HT2C and 5HT1D receptors) reported to increase symptoms in OCD patients and block the anticompulsive‐like effect of serotonin reuptake inhibitors (SRIs) in animal models. The aim of this study was to investigate the interference of CBD on mCPP effects in repetitive burying. Administration of mCPP showed dual effects in the MBT, increasing the number of buried marbles at lower (0.1 mg/kg) while decreasing it at higher doses (1 mg/kg), an effect not related to a general increase in anxiety‐like behavior. As found previously, CBD (30 mg/kg) and the positive control fluoxetine (FLX; 10 mg/kg) decreased burying behavior without changing general exploratory activity. A similar effect was found when subeffective doses of CBD (15 mg/kg) and FLX (3 mg/kg) were administered together. These subeffective doses alone were also able to block mCPP‐induced repetitive burying. The results, in addition to reinforcing a possible anticompulsive effect of CBD, also suggest that mCPP‐induced repetitive burying could be a useful test for the screening of compounds with presumed anticompulsive properties.