Inhibition by ginsenosides Rb1 and Rg1 of cocaine-induced hyperactivity, conditioned place preference, and postsynaptic dopamine receptor supersensitivity in mice

A single or repeated administration of cocaine (15 mg/kg) in mice produced hyperactivity and conditioned place preference (CPP). Ginsenoside Rb-1 (Rb-1) and ginsenoside Rg(1) (Rg(1)), prior to and during the cocaine treatment in mice, inhibited cocaine-induced hyperactivity and CPP. The development of enhanced postsynaptic dopamine (DA) receptor sensitivity in mice displaying a cocaine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine (2 mg/kg). Rb-1 and Rg(1) inhibited the development of postsynaptic DA receptor supersensitivity. However, Rb-1 and Rg(1) did not show any antidopaminergic activity at the postsynaptic DA receptors, because the apomorphine-induced climbing behavior was not inhibited by Rb-1 and Rg(1). Therefore, it is presumed that Rb-1 and Rg(1) modulate DA activity induced by cocaine at the presynaptic DA receptors, and this modulation results in the inhibition of postsynaptic dopaminergic activation. These results suggest that the cocaine-induced CPP may be associated with enhanced DA receptor sensitivity. The inhibition by Rb-1 and Rg(1) of cocaine-induced hyperactivity and CPP may be closely related with the inhibition of dopaminergic activation induced by cocaine at the presynaptic DA receptors. (C) 1999 Elsevier Science Inc.