Acamprosate modulates synaptosomal GABA transmission in chronically alcoholised rats.
Male Sprague-Dawley rats were pulmonary alcoholised for 30 days. Six were treated with acamprosate (400 mg/kg/day, PO) during alcoholisation. The control nonalcoholised group also received acamprosate (400 mg/kg/day, PO) during the 30 days. At the end of the experiment, brains areas (cortex, hippocampus, thalamus, striatum, and olfactory bulbs) were dissected for the study of synaptosomal 3H-GABA uptake. In another experiment, GABA levels were determined in the same areas using HPLC with electrochemical detection. Blood ethanol levels were also measured during alcoholisation. Acamprosate treatment did not modify blood ethanol levels. In cortex and olfactory bulbs, alcoholisation increased 3H-GABA uptake (Vmax) with an increase in the affinity (Km). 3H-GABA uptake was not affected by alcoholisation in other brain areas. In hippocampus and thalamus, acamprosate treatment enhanced 3H-GABA uptake (Vmax) only in alcoholised rats. Moreover, in thalamus, alcoholisation enhanced GABA levels. The effect of alcohol and acamprosate on GABA presynaptic events is discussed and it is concluded that the action of ethanol and acamprosate on GABA transport could be, in part, responsible for the modulation by acamprosate treatment of ethanol behaviour.
Daoust
M
M
Pharmacochimie, U.F.R. Médecine et Pharmacie de Rouen, St. Etienne Du Rouvray, France.
Legrand
E
E
Gewiss
M
M
Heidbreder
C
C
DeWitte
P
P
Tran
G
G
Durbin
P
P
D000077443:Acamprosate; D000437:Alcoholism / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000502:physiology*; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000502:physiology
D014316:Tritium; D013654:Taurine; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D000077443:Acamprosate