Acute effects of ethanol on GABA _A and glycine currents in the lateral habenula neurons of young rats

Abstract

Compelling evidence has shown a pivotal role of dopaminergic function in drug addiction. Recently, the lateral habenula (LHb) has attracted a great deal of attention as another target for abused drugs in the brain because its role in regulating dopaminergic system, among others. GABA and glycine are major inhibitory neurotransmitters. Their corresponding receptors are key targets of ethanol. The properties of these receptors in LHb neurons and their responses to ethanol in particular however, remain unknown. Using the patch clamp techniques, we examined the effects of ethanol on the chloride currents elicited by GABA and glycine in LHb neurons acutely dissociated from 10-20 day-old Sprague–Dawley rats. We show that GABA concentration-dependently elicited a bicuculline sensitive inward current in 96% (130/140) of the neurons tested. Ethanol (43.2 mM) suppressed current elicited by a wide range of concentrations (1-300 μM) of GABA in 74% (35/47) cells tested. Ethanol suppression is dependent on its concentrations but not on membrane potentials of the neurons. Moreover, glycine concentration-dependently elicited an inward current in 94% (112/120) of the neurons tested. Both strychnine and picrotoxin concentration dependently suppressed glycine current with IC ₅₀ of 220 nM and 813 μM, respectively. Ethanol (43.2 mM) potentiated current elicited by unsaturated but not saturated concentrations of glycine. Thus, the LHb neurons of young rats contain both functional GABA _A and glycine receptors which are sensitive to ethanol at pharmacologically relevant concentrations. These effects of ethanol might be important in the control of the activity and output of LHb neurons.