Cannabinoid System of the Lateral Septum in the Modulation of Anxiety-like Behaviors in Rats

Backgrounds: A large body of evidence suggests that the cannabinoid CB1 receptor plays a key role in the regulation of emotional behaviors. The present study was designed to evaluate the effects of CB1 agonist and antagonist on anxiety-like behaviors in the lateral septum (LS) region of the rat brain using elevated plus maze test. Method: Rats were anesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the LS region. After 1 week of recovery, the effects of intra-LS administration of the CB1 receptor agonist, WIN 55,212-2 and CB1 receptor antagonist, AM251, on %OAT and %OAE were measured. Moreover, the effects of pretreatment with AM251 on the response induced by intra-LS administration of WIN 55,212-2 were also assessed. Results: Intra-LS administration of WIN 55,212-2 (0.001, 0.005, and 0.5 mu g/rat) decreased the %OAT and %OAE but not locomotor activity, showing an anxiogenic-like response. Intra-LS injection of different doses of AM251 (0.001, 0.01, and 0.1 mu g/rat) did not significantly alter the anxiety-like parameters on the plus-maze test. However, intra-LS injections of AM251 (0.01 mu g/rat) significantly reversed WIN 55,212-2-induced anxiogenic-like effects. Conclusions: The results suggest that the cannabinoid system of the lateral septum modulates anxiety-like behavior through CB1 receptor.