Likewise, serotonin receptors, a primary target of ethanol action, can modulate GABAA receptor function and expression via PKC-mediated pathways. Activation of 5-HT2 receptors results in inhibition of GABAA receptor-mediated currents that can be blocked by the Ca2+ chelator BAPTA and the receptor for activated C-kinase (RACK) inhibitory peptide (RACK1-rVI) (Feng et al. 2001). In addition, even though 5-HT3 is considered to be an excitatory receptor, it is often expressed on inhibitory GABAergic interneurons, thus activation of 5-HT3 receptors by ethanol may contribute to some of the inhibitory actions of ethanol via increased release of GABA (Lovinger 1999). Furthermore, activation of 5-HT3 receptors is also known to increase the release of dopamine and glutamate (Lovinger 1999). Hence, it is clear that activation of serotonin receptors can alter GABAA receptor function and expression. In addition, recent studies have concluded that dopamine and β-adrenergic receptors can also modulate GABAA receptors via PKA-mediated pathways (Flores-Hernandez et al. 2000). Taken together, it is obvious that receptor cross-talk plays a vital role in modulation of GABAA receptor function and expression following ethanol exposure.
