Changes in dopamine transporter and c-Fos expression in the nucleus accumbens of alcohol-tolerant rats.
BACKGROUND
We have shown that neurochemical functions of 5-HT3 receptors in regulating dopamine (DA) release in the nucleus accumbens (ACC) after alcohol exposure compensate for the dysfunction of serotonergic activity to restore the original properties in processing alcohol tolerance, and that the development of alcohol dependence may be mediated by ACC 5-HT3 receptors. In the present study, the effects of chronic alcohol consumption on the functions of the dopamine transporter (DAT) and the expression of c-Fos proteins were investigated using in vivo brain microdialysis and immunocytochemistry.


METHODS
Perfusion of cocaine and 1-(2-Bis-(4-fluorophenyl) methoxy) ethyl)-4-(3-phenylpropyl) piperizine (GBR 12909) through the microdialysis probe membrane increased the extracellular levels of DA in ACC of alcohol-treated rats that had developed alcohol tolerance by drinking 10% EtOH for 30 days.


RESULTS
The magnitudes of DA reuptake or DAT inhibitors, cocaine, and GBR 12909 that induced DA availability in the ACC were significantly higher in alcohol-treated rats than in controls. When compared with control rats, the alcohol-treated rats exhibited higher levels of DA and its metabolite, DOPAC, in the ACC. Increased expression of the c-Fos-like protein was found in the ACC of alcohol-treated rats. These results show that (1) chronic alcohol consumption desensitizes or decreases the DAT of DA terminals in the ACC and that (2) EtOH causes cellular hyperexcitability of ACC dopaminergic neurons with increased Fos expression during alcohol tolerance.


CONCLUSIONS
The findings suggested that an abnormality of the dopaminergic neurons in the ACC that are involved with DAT dysfunction is associated with the development of alcohol tolerance.
Yoshimoto
K
K
Department of Legal Medicine, Kyoto Prefectural University of Medicine, Japan. kyoshimo@basic.kpu-m.ac.jp
Ueda
S
S
Nishi
M
M
Yang
Y
Y
Matsushita
H
H
Takeuchi
Y
Y
Kato
B
B
Kawai
Y
Y
Noritake
K
K
Kaneda
S
S
Sorimachi
Y
Y
Yasuhara
M
M
D000437:Alcoholism / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism
D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D016760:Proto-Oncogene Proteins c-fos; C493216:Slc6a3 protein, rat; D012701:Serotonin; D000431:Ethanol; C043425:vanoxerine; D003042:Cocaine; D004298:Dopamine