LONG-TERM ETHANOL-CONSUMPTION BY RATS - EFFECT ON ACETYLCHOLINE-RELEASE IN-VIVO, CHOLINE-ACETYLTRANSFERASE ACTIVITY, AND BEHAVIOR

The extent and duration of cholinergic hypofunction induced by long-te rm ethanol consumption was investigated in the rat. Ethanol (20% v/v) was administered to male adult Wistar rats as the sole source of fluid for three or six months. Control rats received tap water. The body we ight, food and fluid intake in ethanol-treated rats were lower than in control rats throughout the treatment. After three months of ethanol consumption, and one week withdrawal, acetylcholine release in freely moving rats, investigated by microdialysis technique coupled to high-p erformance liquid chromotagraphy quantification, was significantly dec reased by 57 and 32% in the hippocampus and cortex, respectively, whil e choline acetyltransferase activity was significantly decreased (-30% ) only in the hippocampus. A complete recovery of choline acetyltransf erase activity and acetylcholine release was found after four ethanol- free weeks. Conversely, after four weeks of withdrawal following six m onths of ethanol treatment, the recovery in acetylcholine release was not accompanied by that in choline acetyltransferase activity, which r emained significantly lower than in control rats in both cortex and hi ppocampus. The ability of rats to negotiate active and passive avoidan ce conditioned response tasks, tested after four ethanol-free weeks, w as strongly impaired in both three- and six-month ethanol-treated rats . In conclusion, our experiments demonstrate that the development of a long-lasting cholingergic hypofunction requires at least six months o f ethanol administration. The hypofunction affects choline acetyltrans ferase activity and acetylcholine release differently, and undergoes a remarkable recovery.