Ethanol‐Induced Increase in Endogenous Dopamine Release May Involve Endogenous Opiates

Abstract

The effect of opiate peptides on basal and potassium-stimulated endogenous dopamine (DA) release from striatal slices was studied in vitro. Dual stimulation of the striatal slices gave a reproducible increase in DA release that was calcium dependent. Addition of the delta-opiate receptor agonists Met5-enkephalin, [D-Ala2,D-Leu5]enkephalin (DADLE), and [D-Ser2]Leu-enkephalin-Thr (DSLET), increased the basal DA release without affecting potassium-stimulated release in a dose-dependent manner. The effect of DADLE was antagonized by the addition of naloxone. In contrast, the mu-opioid receptor agonist [D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAGO) and the epsilon-opioid agonist beta-endorphin inhibited the stimulated DA release without changing the basal release. The inhibitory effect of DAGO on potassium-stimulated release was antagonized by naloxone. The addition of ethanol (75 mM) to the incubation media produced a delayed increase of both the basal and stimulated DA release. There was no change in stimulated DA release when the change in basal release was subtracted, suggesting that ethanol produced a dose-dependent, selective increase in basal DA release. Naloxone and the selective delta-opiate antagonist ICI 174864 inhibited the ethanol-induced increase in basal DA release. Naloxone and ICI 174864 added alone did not alter either basal or stimulated DA release. We therefore suggest that the ethanol-induced increase in basal DA release is an indirect effect involving an endogenous delta-opiate agonist.

Characterization of the decrease of extracellular striatal dopamine induced by intrastriatal morphine administration

“…Some previous studies showed that acute systemic administration of opioids did not increase the release of nigrostriatal DA (Ahtee et al, 1989;Wood & Rao, 1991;Wood & Richard, 1982;Wood et al, 1980;Yonehara & Clouet, 1984). Also, in studies in which DA release was measured from striatal slices, it has been shown that m-opioids somewhat retard the release of DA (Celsen & Kuschinsky, 1974;Kuschinsky et al, 1975;Loh et al, 1976;Schlosser et al, 1995;Widdowson & Holman, 1992). The results of the present study con®rm that there is an inhibitory, naltrexone-sensitive component in the e ect of opioids on striatal DA release.…”

“…d-Opioid receptors are not likely to be involved since they have been shown to either increase striatal DA release in vivo (Dourmap & Costentin, 1994;Dourmap et al, 1992;Pentney & Gratton, 1991) and in vitro Lubetzki et al, 1982;Widdowson & Holman, 1992), or to have no e ect on striatal DA release (Mulder et al, 1984;Scho elmeer et al, 1988). To our knowledge, there is only one study where dopioids were found to inhibit the release of striatal DA in vitro (Schlosser et al, 1995).…”

“…However, contrary to the increase of the acidic DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) we have repeatedly found that the post-mortem concentration of 3-methoxytyramine (3-MT), a metabolite considered to re¯ect the release of DA (for a review see Wood & Altar, 1988) tends to decrease in the striatum of rats or mice given relatively large doses of morphine (Ahtee et al, 1989;Airio & Ahtee, 1997). Morphine (Celsen & Kuschinsky, 1974;Kuschinsky et al, 1975;Marien et al, 1983;Westfall et al, 1983) and the selective m-receptor agonist [DAla 2 , MePhe 4 , Gly-ol 5 ]enkephalin (DAMGO) (Widdowson & Holman, 1992) have been found to decrease the stimulated release of DA from striatal slices as well. Furthermore, there is preliminary evidence that intrastriatally-administered morphine decreases the release of striatal DA in freely moving rats (Rossetti et al, 1990).…”

Plasma concentrations of β-endorphin, adrenocorticotropic hormone, and cortisol in drinking and abstinent chronic alcoholics

“…The association between alcohol and the EOS is apparently mediated by morphine-like substances, also termed tetrahydroisoquinolines (TIQs) (11,15,36,37,40,43), produced from the condensation of acetaldehyde-the main metabolite of ethanol-with dopamine, a neurotransmitter found in elevated concentrations in alcoholics (4,49). However, another study has refuted this mechanism (42).…”

Effect of acute alcohol intoxication on the opioid system in humans

“…The effects of alcohol on the central nervous system in AAI have been investigated from several approaches, including its influence on the cell membrane (12,33,44), and more specifically, its effect on three types of neurotransmitter: opioid peptides (7,8,21,23,47), GABA (29,31), and catecholamines (11,32). Although the effects of alcohol on the cell membrane are well known, its effect on specific neurotransmitters is controversial, particularly in the case of endogenous opioids (19).…”