Abstract

It has been suggested that GABAergic neurotransmission can modulate cocaine dependence and seizure activity. Since Gastrodia elata Bl (GE), an oriental herb agent, has been shown to enhance GABAergic transmission, we examined whether GE affects cocaine-induced seizures, conditioned place preference (CPP), and behavioral sensitization in mice. Treatment with GE (500 or 1000 mg/kg, p.o.) significantly delayed seizure onset time and significantly shortened seizure duration induced by cocaine (90 mg/kg, i.p.). In addition, cocaine (15 mg/kg, i.p.)-induced CPP was significantly attenuated by GE in a dose-dependent manner. However, GE did not significantly alter behavioral sensitization induced by cocaine (15 mg/kg, i.p.). In order to understand whether GABAergic receptors are implicated in GE-mediated pharmacological action in response to cocaine, GABAA receptor antagonist bicuculline and GABAB receptor antagonist SCH 50911 were employed in the present study. GE-mediated attenuations on the cocaine-induced seizures and CPP were significantly reversed by bicuculline (0.25 or 0.5 mg/kg, i.p.), but not by SCH 50911 (1.5 or 3.0 mg/kg, i.p.). Therefore, our results suggest that GE attenuates cocaine-induced seizures and CPP via, at least in part, GABAA receptor activation.

Highlights

  • Since GABA-mimetic drugs and GABAergic agonists have shown to attenuate behavioral sensitization or seizures induced by cocaine [18, 19], we examined whether Gastrodia elata Bl (GE) affects cocaine-induced seizures, conditioned place preference (CPP), and behavioral sensitization in mice

  • Since GE has been reported to enhance GABAergic neurotransmission, we applied GABAA receptor antagonist bicuculline and GABAB receptor antagonist SCH 50911 to understand whether GABAergic receptors are involved in the anti-convulsive effect of GE against cocaine toxicity

  • GEmediated anticonvulsant effect was significantly reversed by bicuculline [for both of seizure latency and seizure duration: bicuculline (0.5 mg/kg) + GE (1000 mg/kg) + cocaine vs. saline + GE (1000 mg/kg) + cocaine, P < 0.01] in a doserelated manner, but not by SCH 50911, suggesting that GE attenuates cocaine-induced seizures, at least in part, via GABAA receptors activation (Fig. 3A and B)

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Summary

Introduction

Previous studies have shown that cocaine-induced seizures can be mediated by enhanced dopaminergic and glutamatergic transmissions [7] and reduced GABAergic transmission [8]. Earlier study suggested that activation of GABAA receptor is important for GE-mediated anxiolytic effect in mice [12].

Results
Conclusion
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