Involvement of GABAergic systems and benzodiazepine receptors in the jumping behavior induced by harmine and apomorphine in rats.

Abstract

Harmine (HA) induces a jumping behavior in rats when the central dopaminergic function has been activated. Possible involvement of the GABAergic systems and the benzodiazepine receptors (BZA-R) in the jumping behavior induced by HA and apomorphine (APO) was investigated. Pretreatment with GABAergic agonists, muscimol (0.05-0.2 mg/kg) and diazepam (0.2-1.0 mg/kg), and antagonists, picrotoxin (0.1-0.5 mg/kg) and bicuculline (0.1-0.5 mg/kg), suppressed the jumping behavior in a dose-dependent manner in rats treated with HA (10 mg/kg) and APO (2 mg/kg). After treatment with 2, 5 or 10 mg/kg of HA in combination with 2 mg/kg of APO, a decrease in 3H-diazepam binding to the brain regional membranes was observed in the corpus striatum (CS) in a dose-dependent manner, but not in the other brain regions. The decrease in the 3H-diazepam binding to the CS membranes was proportional to the increase in the HA levels in the CS, and the HA levels were correlated with the intensity of jumping behavior. Pretreatment with Ro 15-1788, an antagonist of BZA-R, suppressed the jumping behavior induced by HA and APO. These results indicated the involvement of the GABAergic systems in the jumping behavior and suggested that HA induced the jumping behavior partly as a result of interacting with the BZA-R.