Abstract
We studied the effects of ethanol on concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5-HT) and their metabolites in rat hippocampus and striatum. Ethanol (2 or 4 g/kg, po, from a 20% aqueous solution) was administered daily to male Wistar rats (4-13 per group) for 30 days and animals were sacrificed 30 min or 48 h after the last administration. Monoamines were measured by HPLC and considered significant at P < 0.05. A 47% increase in 5-HT levels was observed in the hippocampus with 4 g/kg ethanol in the 30-min protocol. Ethanol (2 and 4 g/kg) decreased DA (2114.5 +/- 126.4 and 1785.1 +/- 234.2 ng/g wet tissue, respectively) and 3,4-dihydroxyphenylacetic acid (DOPAC, 1477.6 +/- 132.1 and 1218.8 +/- 271.7 ng/g wet tissue, respectively) levels, while the higher dose also decreased NE (159.8 +/- 13.5), 5-HT (228.0 +/- 46.8) and 5-hydroxy-3-indoleacetic acid (5-HIAA, 304.4 +/- 37.2 ng/g wet tissue), in the striatum after a 48-h withdrawal as compared to controls (DA: 3063.9 +/- 321.3; DOPAC: 2379.6 +/- 256.0; NE: 292.8 +/- 50.2; 5-HT: 412.4 +/- 36.2; 5-HIAA: 703.9 +/- 61.4 ng/g wet tissue). In the 30-min protocol, ethanol (2 or 4 g/kg) decreased striatal NE (66 and 70%) and DA (50 and 36%) levels. On the other hand, increases were seen in 5-HIAA (146 and 153%) and 5-HT (59 and 86%) levels. Ethanol (2 g/kg, po) increased the homovanillic acid (HVA)/DA ratio (129%) in the striatum in the 30-min protocol, while at the higher dose it increased the HVA/DA ratio in the 48-h protocol (61%). These results indicate alterations in monoamines, mainly in the striatum, after chronic ethanol, which are influenced by dose and by the length of time after the last drug administration.
Highlights
Acute or chronic ethanol ingestion has been shown to induce significant changes in neurotransmitter systems (1-3)
A significant change was observed in 5-HT levels with the higher dose compared to control and to the lower ethanol dose [F(2,9) = 7.041, P = 0.0144] in the 30-min protocol
We showed that rats chronically exposed to ethanol presented significant alterations in the levels of monoamines and metabolites in both the hippocampus and striatum
Summary
Acute or chronic ethanol ingestion has been shown to induce significant changes in neurotransmitter systems (1-3). Dopamine (DA) and 5-hydroxytryptamine (5HT) have received special attention because of their putative role in the motivational effects of ethanol (4-6). Administration of ethanol induces DA release (1,7,8) in the caudate nucleus and nucleus accumbens of freely moving rats, but the mechanisms responsible for this action remain to be defined (9). Clinical studies indicate that 5-HT re-uptake inhibitors exhibit some efficacy in reducing alcoholism (12). The site of action of the 5-HT re-uptake inhibitors is unknown, but it is possible that these agents act somewhere in central reward pathways to modify the action of ethanol (13). Ethanol is known to affect the release of noradrenaline, but this effect is probably dependent on the duration of the drug intake (14)
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