Ethanol potentiates both GABAergic and glutamatergic signaling in the lateral habenula.

摘要: Ethanol's aversive property may limit it's use, but the underlying mechanisms are no well-understood. Emerging evidence suggests a critical role for lateral habenula (LHb) in response to various drugs, including ethanol. We previously showed that ethanol enhances glutamatergic transmission and stimulates LHb neurons. GABAergic transmission, major target of many brain regions, also tightly regulates activity. This study assessed action on rat slices. Application accelerated spontaneous potential firing neurons, activity was increased by GABAA receptor antagonist gabazine, ethanol-induced acceleration further gabazine. Additionally, potentiated (inhibitory postsynaptic currents, IPSCs) with an EC50 1.5 mM. Ethanol-induced potentiation IPSCs GABAB antagonist; it mimicked dopamine, dopamine agonists, reuptake blocker, completely prevented reserpine, which depletes store catecholamine. Moreover, involved cAMP signaling. Finally, enhanced simultaneously transmissions majority neurons: former being greater than latter, net effect firing. Since excitation contribute aversion, inhibition tends reduce aversion.