FIGURE 3.

Uncontrolled opening of hemichannels/pannexons and their effect on neuronal circuits that govern ethanol consumption. (A) One mechanism by which glial hemichannels or pannexons may increase ventral tegmental area (VTA) dopaminergic neuron activity and nucleus accumbens (NAc) dopamine (DA) levels involves the synaptic release of glutamate via these channels. Stimulation of NMDARs could then augment VTA dopaminergic activity and trigger the firing of GABAergic neurons in the NAc, increasing alcohol consumption. (B) In addition, increased glutamate released from glial hemichannels and pannexons may enhance DA levels at the NAc by activation of unknown glutamate receptors on presynaptic dopaminergic terminals at the VTA. Potentiated activation of dopaminergic D1or D2 receptors (D1R/D2R) on medium spiny neurons (MSNs) at the NAc may then promote alcohol consumption. (C) Finally, taurine release through astroglial Cx43 hemichannels may activate glycine receptors on MSNs GABAergic neurons, decreasing their inhibitory tone on VTA dopaminergic neurons.