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 cytoskeleton undergo profound changes following chronic alcohol use and misuse. Here we studied the expression of the neuronal cytoskeletal microtubule-associated protein 2 (MAP2) following long-term alcohol consumption and subsequent alcohol withdrawal. Alcohol-preferring AA (Alko Alkohol) rats with a high voluntary alcohol consumption for a period of 16 months were compared with age-matched control rats without prior experience with alcohol. For comparison, in a second experiment, heterogeneous Wistar rats that also had voluntary access to alcohol for 8 months were examined following alcohol consumption and withdrawal. In situ hybridization and subsequent dot blot and Northern blot analysis for further quantification revealed that chronically alcoholized animals exhibit markedly decreased MAP2 mRNA levels in several parts of the extrapyramidal system (mainly in the caudate putamen, the substantia nigra pars compacta and the globus pallidus), the mesolimbic system, in several hypothalamic nuclei and in the nucleus inferior colliculus. Other areas such as the hippocampus, frontoparietal cortex and cerebellum were less affected by chronic alcohol intake, however, in these regions the MAP2 mRNA levels were increased during alcohol withdrawal. These results suggest that long- term alcohol self-administration affects central neurons involved in motor control via the influence on the integrity of the cytoskeleton and may thus induce motor dysfunction.