A low chronic ethanol exposure induces morphological changes in the adolescent rat brain that are not fully recovered even after a long abstinence: an immunohistochemical study

Exp Neurol. 2006 Aug;200(2):438-59. doi: 10.1016/j.expneurol.2006.03.001. Epub 2006 Apr 21.


Little is known about the morphological effects of alcoholism on the developing adolescent brain and its consequences into adulthood. We studied here the relationship between two neurotransmitter systems (the serotoninergic and nitrergic) and the astrocytic and neuronal cytoskeleton immediately and long after drinking cessation of a chronic, but low, ethanol administration. Adolescent male Wistar rats were exposed to ethanol 6.6% (v/v) in drinking water for 6 weeks and studied after ending exposure or after a 10-week recovery period drinking water. Control animals received water. Brain sections were processed by immunohistochemistry using antibodies to serotonin (5-HT); glial fibrillary acidic protein (GFAP); astroglial S-100b protein; microtubule associated protein-2 (MAP-2); 200 kDa neurofilaments (Nf-200); and neuronal nitric oxide synthase (nNOS). The mesencephalic dorsal and median raphe nucleus (DRN; MRN) and three prosencephalic areas closely related to cognitive abilities (CA1 hippocampal area, striatum and frontal cortex) were studied by digital image analysis. 5-HT immunoreactivity (-ir) decreased in the DRN and recovered after abstinence and was not changed in the MRN. In the three prosencephalic areas, astrocytes' cell area (GFAP-ir cells) increased after EtOH exposure and tended to return to normality after abstinence, while cytoplasmic astroglial S100b protein-ir, relative area of MAP-2-ir and Nf-200-ir fibers decreased, and later partially recovered. In the striatum and frontal cortex, nNOS-ir decreased only after abstinence. In conclusion, in the adolescent brain, drinking cessation can partially ameliorate the ethanol-induced morphological changes on neurons and astrocytes but cannot fully return it to the basal state.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / metabolism
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Brain / cytology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Chemistry / drug effects
  • Cell Count / methods
  • Central Nervous System Depressants / administration & dosage*
  • Central Nervous System Depressants / blood
  • Diagnostic Imaging / methods
  • Ethanol / administration & dosage*
  • Ethanol / blood
  • Gene Expression / drug effects
  • Immunohistochemistry
  • Male
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors


  • Central Nervous System Depressants
  • Nerve Tissue Proteins
  • Ethanol