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Chunk #84 — Alcohol tolerance mechanisms — Tolerance and altered GABAA receptor function and regulation

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The role of GABA(A) receptors in the acute and chronic effects of ethanol: a decade of progress.
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mIPSC response to ethanol and decreased response to diazepam (Liang et al. 2007), suggesting that the observed changes in receptor expression might underlie altered sensitivity to ethanol. Furthermore, chronic ethanol exposure altered the recovery of baseline spontaneous neural activity of medial septal/diagonal band of Broca neurons following GABA microiontophoresis (Matthews et al. 2000a). These studies suggest that the observed changes in receptor expression following chronic ethanol exposure might underlie altered sensitivity to ethanol and GABA. Interestingly, the mIPSC effects were transient, and responses returned to normal after 2 weeks. It is possible that these transient changes contribute to ethanol tolerance. Tolerance may be restricted to selected brain regions or cell populations. Tolerance to ethanol’s effects in the CA3 region of neonatal rats does not occur in slices exposed to ethanol for a prolonged period (Galindo and Valenzuela 2006). Finally, inhibition of synaptic GABAA receptors results in the incorporation of receptors diffusing from peri- and extrasynaptic sites (Thomas et al. 2005), independent of receptors arising from intracellular stores. Overall, while not pinpointing the exact role of GABAA receptors in ethanol action, these studies lend support to a possible role of changes in GABAA receptor subtype expression contributing to tolerance to various