High ethanol sensitive glycine receptors regulate firing in D1 medium spiny neurons in the nucleus accumbens

Abstract Inhibitory glycine receptors (GlyRs) are widely expressed in spinal cord and brain stem. They are also expressed in the nucleus Accumbens (nAc) where they have been implicated in the release of dopamine from the ventral tegmental area to the nAc in the presence of ethanol. One of the major types of neurons in the nAc are the Dopamine 1 receptor-expressing (D1+) medium spiny neurons (MSNs) that are activated when addictive drugs, like ethanol, are administrated. Thus, D1(+) MSNs are a relevant target for the study of ethanol effects. Here, using electrophysiological recordings, we report that GlyRs in D1(+) MSNs are highly sensitive to ethanol, with potentiation starting at 5 mM (26 ± 5%). Single channel recordings in D1(+) MSNs showed that 10 mM ethanol increased the open probability of the channel (0.22 ± 0.05 versus 0.66 ± 0.16), but did not affect channel conductance (~40 pS). A glycinergic mediated tonic current in D1(+) MSNs was potentiated by 10 and 50 mM ethanol causing a reduction in the excitability of these cells. A 34 ± 7% reduction in action potential firing was observed in these neurons in the presence of 50 mM ethanol. Interestingly, no effects of ethanol were detected in the presence of strychnine or in D1(-) MSNs in the nAc. These results indicate that GlyRs present in D1(+) MSNs are sensitive to low concentrations of ethanol, and that potentiation of this inhibitory current regulates the activation of nAc, acting as a homeostatic signal that would prevent over-activation of the reward system when drugs like ethanol are consumed.