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Abstract
We studied the effects of ethanol on the levels of norepinephrine, dopamine, serotonin (5-HT) and their metabolites as well as on D1- and D2-like receptors in the rat striatum. Ethanol (2 or 4 g/kg, po) was administered daily by gavage to male Wistar rats and on the 7th day, 30 min or 48 h after drug administration, the striatum was dissected for biochemical assays. Monoamine and metabolite concentrations were measured by HPLC and D1- and D2-like receptor densities were determined by binding assays. Scatchard analyses showed decreases of 30 and 43%, respectively, in D1- and D2-like receptor densities and no change in dissociation constants (Kd) 48 h after the withdrawal of the dose of 4 g/kg. Ethanol, 2 g/kg, was effective only on the density of D2-like receptors but not on Kd of either receptor. Thirty minutes after the last ethanol injection (4 g/kg), decreases of D2 receptor density (45%) as well as of Kd values (34%) were detected. However, there was no significant effect on D1-like receptor density and a 46% decrease was observed in Kd. An increase in dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), a decrease in norepinephrine, and no alteration in 5-HT levels were demonstrated after 48-h withdrawal of 4 g/kg ethanol. Similar effects were observed in dopamine and DOPAC levels 30 min after drug administration. No alteration in norepinephrine concentration and a decrease in 5-HT levels were seen 30 min after ethanol (4 g/kg) administration. Our findings indicate the involvement of the monoaminergic system in the responses to ethanol.
Highlights
Acute or chronic alcohol consumption interferes differentially with transmission processes in the central nervous system, affecting many if not all of the known neurotransmitter systems [1]
Scatchard analyses (Table 1) of the [3H]SCH-23390 binding data for rat striatum showed a significant [F(2,12) = 6.026, P = 0.0192] decrease of D1-like receptor density (Bmax) only with the high dose of ethanol and the 48-h withdrawal, but there was no alteration in the Kd compared to controls
No effect was observed on D1 receptor density [t(9) = 1.018, P = 0.3353], but the Kd value was decreased by 46% [t(9) = 4.173, P = 0.0024] (Table 3)
Summary
Acute or chronic alcohol consumption interferes differentially with transmission processes in the central nervous system, affecting many if not all of the known neurotransmitter systems [1]. The results of studies of the effects of repeated ethanol administration on dopaminergic D1- and D2-like receptors appear contradictory and inconclusive. Lograno et al [3] demonstrated that an 8-week ethanol treatment (3%, v/v) increases the number of dopamine D1 receptor sites in the rat caudate putamen with no alteration in D2 receptor density. Hruska [4] observed that ethanol administered in a completely liquid diet for 21 days produced an increase in the density of striatal D1 or D2 receptors without altering receptor affinity. Lucchi et al [6] observed that chronic exposure to ethanol (6% in drinking water for 25 days) decreased the density of both D1 and D2 receptors in rat striatal membranes
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Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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