European journal of pharmacology
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Comparative Study
Up-regulation of cortical AMPA receptor binding in the fawn-hooded rat following ethanol withdrawal.
The present study has employed quantitative receptor autoradiography to compare the binding of (S)-[3H]5-fluorowillardiine to (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in the brains of alcohol-preferring Fawn-Hooded (FH) rats, alcohol non-preferring Wistar-Kyoto (WKY) rats, and FH rats following a 28-day period of 5% ethanol consumption with or without ethanol withdrawal. Significantly higher binding of [3H]5-fluorowillardiine was found in the cingulate cortex (+12%) and claustrum (+13%) in alcohol naïve FH rats compared to WKY rats. ⋯ In contrast, ethanol withdrawal induced a significant "rebound" increase in binding by +22% in frontal and parietal cortex, by +17% in cingulate cortex and +13% in claustrum, and by +14% in the septohippocampal nucleus compared to chronic ethanol-exposed FH rats. The findings suggest that AMPA receptors in frontal cortical regions are sensitive to ethanol and therefore may be implicated in the predisposition of alcohol preference in FH rats.
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The ATP-gated K(+) channel openers diazoxide, levcromakalim and morphine induce cell hyperpolarization by opening the K(+) channels and enhancing K(+) efflux. This hyperpolarization decreases intracellular Ca(2+) levels, lessening neurotransmitter release thus leading to antinociception. ⋯ Antisense to all three opioid receptors attenuated the effect of diazoxide, suggesting that diazoxide is inducing the release of endogenous opioids activating the mu(MOR-1)-, delta(DOR-1)-, and kappa(KOR-1)-opioid receptors. Antisense to the mu-opioid receptor clone and delta-opioid receptor clone attenuated levcromakalim-induced antinociception, indicating that endogenous opioids acting at the mu- and delta-opioid receptors are potential candidates for the mediation of the antinociceptive effects of levcromakalim.