• Energy Research

The effect of ethanol administration on the in vitro release of alpha-neoendorphin (ANEO) and Met-enkephalin-Arg6-Gly7-Leu8 (MEAGL), peptides derived from prodynorphin and proenkephalin, respectively, was studied in the rat hypothalamus. Single ethanol administration had no effect on the tissue level and potassium-stimulated release of these peptides. Repeated ethanol administration increased the release of ANEO and reduced the release of MEAGL from hypothalamic slices. Two days after cessation of ethanol administration the release of MEAGL returned to control values, whereas the release of ANEO was significantly inhibited. On the other hand, the tissue level of those peptides remained unchanged after repeated ethanol or 2 days after its last administration. The present study shows that repeated treatment with ethanol may lead to an increase in the prodynorphin neurons' sensitivity to the depolarizing effect of potassium. In contrast, the sensitivity of the proenkephalin system to ethanol seems to be inhibited. Thus, ethanol appears to have an opposite effect on the sensitivity of hypothalamic proenkephalin and prodynorphin neurons.

The present study was carried out to evaluate the effect of morphine, cocaine and ethanol on the density of opioid receptors in the nucleus accumbens and striatum of rat brain. The animals were injected i.p. with morphine in a single dose 20 mg/kg, or twice daily for 10 days in increasing doses of 20-100 mg/kg. Cocaine was administered in a dose of 60 mg/kg/day following the "binge" paradigm, every hour for 3 h, one day (single treatment) or five days (chronic treatment). Ethanol was administered in drinking water at increasing concentrations of 1-6% v/v, for one month. As shown by receptor autoradiography, single morphine and cocaine administration did not influence the binding density of the selective ligand of delta2 receptors [3H]Ile5,6deltorphin b, but single administration of cocaine decreased binding density of a highly selective antagonist of delta receptors, [3H]H-Tyr-Tic psi[CH2-NH]Phe-Phe-OH. Repeated morphine administration decreased the receptor density after both ligands of the delta receptor in the nucleus accumbens after 3, 24 and 48 h, and in the striatum after 24 and 48 h. The density of [3H]Ile5,6deltorphin b binding remained unchanged in both structures following repeated cocaine administration. After repeated cocaine administration either no changes (3 h) or a decrease in the binding of [3H]H-Tyr-Tic psi[CH2-NH]Phe-Phe-OH in the nucleus accumbens and striatum were observed after 24 and 48 h. Ethanol did not influence the binding density of [3H]H-Tyr-Tic psi[CH2-NH]Phe-Phe-OH and [3H]Ile5,6deltorphin b in the nucleus accumbens and striatum at any time-point studied. In the nucleus accumbens and striatum, no changes were found in the binding density of [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol following single or repeated morphine administration. At 3 h after single or repeated "binge" cocaine administration, the binding of [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol was not changed in either structure, but after 24 h the density of mu opioid receptors was decreased in both structures. Ethanol given to rats in drinking water decreased the binding of [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol at the time of exposure to ethanol, yet in the nucleus accumbens only. Ethanol withdrawal decreased the density of the mu receptor in both structures after 24, 48 and 96 h. The above data indicate that repeated administration of morphine evokes a long-lasting down-regulation of the density of delta1 and delta2 opioid receptors, whereas cocaine affects in a similar way only the delta1 subtype in the nucleus accumbens, and to a lesser extent in the striatum. A long-term intake of ethanol solution down-regulates mu opioid receptors in both structures, but has no effect on any type of delta receptors. Thus changes in the particular opioid receptor depend on the type of drug used. Furthermore, the most profound changes are observed after late withdrawal, which may play some role in maintaining the state of dependence.

The effect of single and repeated (19 days) intragastric ethanol administration on prodynorphin mRNA and alpha-neoendorphin levels in the hippocampus of the rat was studied using in situ hybridization and RIA methods, respectively. Single ethanol administration had no effect on either of these two parameters. Repeated ethanol administration decreased both immunoreactive (ir) alpha-neoendorphin (by ca. 37%) and prodynorphin mRNA (by ca. 57%) levels. Two days after the last dose of ethanol no changes in the ir-alpha-neoendorphin tissue content were found, whereas the level of prodynorphin mRNA remained decreased (by ca. 44%). These results suggest that repeated ethanol evokes a long-lasting decrease in the biosynthesis of hippocampal prodynorphin, this effect that may play some role in the ethanol-induced deficiency of neuronal functions.