CB1-RECEPTOR ANTAGONIST SR-141716A MODULATES LOCOMOTOR ACTIVITY IN OBX-RATS

Dysfunction of the endocannabinoid system has been related to depressive-like behavior. In our study, bilateral olfactory bulbectomy (OBX) was used as an animal model of depression. We evaluated the effect of the selective CB1-antagonist SR-141716A (Rimonabant) on the exploratory and locomotor activity of OBX-rats. Rimonabant was administered intragastrically for 14 days to OBX-rats, divided into 3 experimental groups, where the drug was given before; immediately (1-14 days) after; or 14 days (14-28 day) after OBX. Exploratory and locomotor activity of OBX-rats was tested in an Opto-Varimex apparatus. SR-141716A, administered subchronically, intragastrically exerted locomotor stimulating effects in OBX- and sham-operated rats, while the exploratory activity was not affected. The time interval for the drug administration is of significance for the manifestation of the effects on locomotor activity in OBX-rats. SR-141716A applied 14 days before OBX or after the development of a depressive-like state (14-28 days after OBX), but not immediately after OBX (1-14 days) aggravated the OBX-induced hyperlocomotor state.