The effects of chronic ethanol consumption on the mesolimbic and nigrostriatal dopamine systems.
Both the mesolimbic dopamine system, which is involved with the rewarding properties of several drugs of abuse, and the nigrostriatal dopamine system, which is involved with motor function, appear to be sensitive to the effects of ethanol. In order to determine which components of the mesolimbic and nigrostriatal dopamine systems are adversely affected by chronic ethanol consumption, we assessed dopamine and DOPAC (3,4-dihydroxyphenylacetic acid) concentration and D1 and D2 receptors in several dopaminergic brain areas. These studies demonstrated that consumption of a 6.6% (v/v) ethanol-containing lipid diet for 1 month affected several components of the mesolimbic dopamine system in 3-month-old Fisher 344 rats and fewer components of the nigrostriatal dopamine system. Specifically, there was a 1.6- to 2.6-fold increase in the concentration of DOPAC in the nucleus accumbens (NA), frontal cortex (FCX), ventral tegmental area (VTA), and substantia nigra (SN). While the increase in DOPAC in the FCX and VTA was paralleled by a similar increase in dopamine, there was a significant deficiency of dopamine in the SN. These results suggest that there is an increase in dopamine turnover in the FCX, VTA, NA, and SN, which is accompanied by increased dopamine synthesis in the former two regions. Studies of dopamine receptors in control and ethanol-fed rats demonstrated a 25% loss of D1 receptors in the NA. No significant differences were found in D1 receptors in the striatum or globus pallidus. In addition, there were no differences in the number of total D2 receptors or in the conversion of the high to low affinity state of D2 receptors in the nucleus accumbens and striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
Pellegrino
S M
SM
Department of Molecular and Cellular Biochemistry, Loyola University of Chicago, Stritch School of Medicine, Maywood, IL 60153.
Druse
M J
MJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001552:Benzazepines / Q000493:pharmacokinetics; D001931:Brain Mapping; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D000431:Ethanol / Q000493:pharmacokinetics; D005917:Globus Pallidus / Q000187:drug effects / Q000502:physiology; D008032:Limbic System / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000503:physiopathology; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000493:pharmacokinetics; D013378:Substantia Nigra / Q000187:drug effects* / Q000503:physiopathology
D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D000431:Ethanol; D013134:Spiperone; D004298:Dopamine