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 Rb1 (Rb1) and ginsenoside Rg1 (Rg1), 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). Rb1 and Rg1 inhibited the development of postsynaptic DA receptor supersensitivity. However, Rb1 and Rg1 did not show any antidopaminergic activity at the postsynaptic DA receptors, because the apomorphine-induced climbing behavior was not inhibited by Rb1 and Rg1. Therefore, it is presumed that Rb1 and Rg1 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 Rb1 and Rg1 of cocaine-induced hyperactivity and CPP may be closely related with the inhibition of dopaminergic activation induced by cocaine at the presynaptic DA receptors.
Kim
H S
HS
Department of Pharmacology, College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
Kim
K S
KS
Oh
K W
KW
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D036145:Ginsenosides; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D005894:Panax / Q000737:chemistry*; D010946:Plants, Medicinal; D011954:Receptors, Dopamine / Q000187:drug effects*; D012503:Saponins / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects
D002491:Central Nervous System Agents; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D036145:Ginsenosides; D011954:Receptors, Dopamine; D012503:Saponins; D003042:Cocaine; D001058:Apomorphine; C035054:ginsenoside Rg1