Clomipramine increases the striatal concentrations of dopamine and homovanillic acid in rats chronically consuming alcohol.
OBJECTIVE
There have been many studies on the relationships between the dopaminergic system, alcoholism and antidepressant drugs; the information, however, is controversial. The purpose of this study was to examine the effect of clomipramine (CMI), a tricyclic antidepressant, on the striatal concentration of dopamine (DA) and homovanillic acid (HVA), and their turnover, in a rat model of chronic alcohol ingestion.


METHODS
After 10 months of exposure to either water (expW) or alcohol (expA), female Wistar rats (N = 60) were randomly assigned to one of the following six groups: (1) (expW) control group (C), normal diet; (2) (expA) alcohol administration group (A), drinking water was replaced by commercial brandy that was 38% ethanol; (3) (expW) clomipramine group (CMI), received intraperitoneal injections over 4 months; (4) (expA) alcohol administration + clomipramine group (ACMI); (5) (expA) alcohol abstinence group (AA); and (6) (expA) alcohol abstinence + clomipramine group (AACMI). Each group consisted of 10 animals.


RESULTS
Chronic alcohol intake decreased striatal dopamine concentration (p < .001), whereas clomipramine administration produced a significant increase (p < .001) when administered in both control rats and rats exposed to long-term alcohol administration. The increase in the ACMI group was significantly different (p < .001) when it was compared with the CMI group. In the AA and AACMI groups, a significant decrease of striatal dopamine was observed (p < .001). During long-term alcohol administration, homovanillic acid decreased (p < .005). HVA/DA ratio increased in AA and AACMI groups (p < .001).


CONCLUSIONS
These findings show that clomipramine produces favorable changes in dopaminergic systems altered by chronic alcohol administration. Results also provide evidence to support further prospective studies of potential therapeutic effects of antidepressant drugs in alcoholism.
Palencia
G
G
Department of Neuroimmunology, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, DF. gpalencia_2000@yahoo.com
Rios
C
C
Sotelo
J
J
D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine; D004298:Dopamine; D006719:Homovanillic Acid