• anticonvulsant;
  • dopamine;
  • EPSC;
  • GABAB receptors;
  • α2-adrenoceptors


We recently reported that anticonvulsant anilino enaminones depress excitatory postsynaptic currents (EPSCs) in the nucleus accumbens (NAc) indirectly via γ-aminobutyric acid (GABA) acting on GABAB receptors [S.B. Kombian et al. (2005)Br. J. Pharmacol., 145, 945–953]. Norepinephrine (NE) and dopamine (DA), both known to be involved in seizure disorders, also depress EPSCs in this nucleus. The current study explored a possible interaction between enaminones and adrenergic and/or dopaminergic mechanisms that may contribute to their synaptic depression and anticonvulsant effect. Using whole-cell recording in rat forebrain slices containing the NAc, we show that NE-induced, but not DA-induced, EPSC depression occludes E139-induced EPSC depressant effect. UK14,304, a selective α2 receptor agonist, mimicked the synaptic effect of NE and also occluded E139 effects. Phentolamine, a non-selective α-adrenergic antagonist that blocked NE-induced EPSC depression, also blocked the E139-induced EPSC depression. Furthermore, yohimbine, an α2-adrenoceptor antagonist, also blocked the E139-induced EPSC depression, while prazosin, a selective α1-adrenergic antagonist, and propranolol, a non-selective β-adrenoceptor antagonist, did not block the E139 effect. Similar to the E139-induced EPSC depression, the NE-induced EPSC depression was also blocked by the GABAB receptor antagonist, CGP55845. By contrast, however, neither SCH23390 nor sulpiride, D1-like and D2-like DA receptor antagonists, respectively, blocked the E139-induced synaptic depression. These results suggest that NE and E139, but not DA, employ a similar mechanism to depress EPSCs in the NAc, and support the hypothesis that E139, like NE, may act on α2-adrenoceptors to cause the release of GABA, which then mediates synaptic depression via GABAB receptors.