LONG-TERM ALCOHOL SELF-ADMINISTRATION AND ALCOHOL-WITHDRAWAL DIFFERENTIALLY MODULATE MICROTUBULE-ASSOCIATED PROTEIN-2 (MAP2) GENE-EXPRESSION IN THE RAT-BRAIN

Chronic alcohol intoxication is known to produce neuronal degeneration in the central and peripheral nervous system of experimental animals and of humans. It is suggested that various components of the cytoskel eton undergo profound changes following chronic alcohol use and misuse . Here we studied the expression of the neuronal cytoskeletal microtub ule-associated protein 2 (MAP2) following long-term alcohol consumptio n and subsequent alcohol withdrawal. Alcohol-preferring AA (Alko Alkoh ol) rats with a high voluntary alcohol consumption for a period of 16 months were compared with age-matched control rats without prior exper ience with alcohol. For comparison, in a second experiment, heterogene ous Wistar rats that also had voluntary access to alcohol for 8 months were examined following alcohol consumption and withdrawal. In situ h ybridization and subsequent dot blot and Northern blot analysis for fu rther quantification revealed that chronically alcoholized animals exh ibit markedly decreased MAP2 mRNA levels in several parts of the extra pyramidal system (mainly in the caudate putamen, the substantia nigra pars compacta and the globus pallidus), the mesolimbic system, in seve ral hypothalamic nuclei and in the nucleus inferior colliculus. Other areas such as the hippocampus, frontoparietal cortex and cerebellum we re less affected by chronic alcohol intake, however, in these regions the MAP2 mRNA levels were increased during alcohol withdrawal. These r esults suggest that long-term alcohol self-administration affects cent ral neurons involved in motor control via the influence on the integri ty of the cytoskeleton and may thus induce motor dysfunction. (C) 1998 Elsevier Science B.V. All rights reserved.