The anti-craving drug acamprosate reduces c-fos expression in rats undergoing ethanol withdrawal.
Acamprosate (Ca salt of N-acetylhomotaurine) is a novel anti-craving substance which a double-blind placebo-controlled study has proven to be therapeutically useful in the prevention of relapses in weaned alcoholics. In the present study the expression of the immediate-early gene c-fos in rat hippocampal and cerebellar neurons was used to monitor the modulatory effect of acamprosate on neuronal excitability during ethanol withdrawal. Several hybridization techniques were employed to investigate the effect of acamprosate on c-fos expression. Acamprosate (200 mg/kg; intraperitoneally) reduced the elevated c-fos mRNA levels in the hippocampus and the cerebellum following 24 h of ethanol withdrawal, or the application of the convulsant pentylenetetrazole. The effect of ethanol withdrawal on c-fos expression was more pronounced in the cerebellum than in the hippocampus. In the hippocampus (CA1) and the cerebellum acamprosate alone induced a significant increase in c-fos expression in drug-naive animals. Only in the hippocampus did co-administration of pentylenetetrazole during ethanol withdrawal induce a further increase in c-fos expression. The present findings support the notion that acamprosate elicits its preventive effect on relapse by reducing the hyperexcitability of central neurons during withdrawal, following long-term ethanol consumption.
Putzke
J
J
Clinical Institute, Max-Planck-Institute of Psychiatry, Munich, Germany. putzke@mpipsykl.mpg.de
Spanagel
R
R
Tölle
T R
TR
Zieglgänsberger
W
W
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015151:Immunoblotting; D017403:In Situ Hybridization; D008297:Male; D015345:Oligonucleotide Probes / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D003292:Convulsants; D015345:Oligonucleotide Probes; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D013654:Taurine; D000431:Ethanol; D000077443:Acamprosate; D010433:Pentylenetetrazole