Lower packing density of glial fibrillary acidic protein-immunoreactive astrocytes in the prelimbic cortex of alcohol-naive and alcohol-drinking alcohol-preferring rats as compared with alcohol-nonpreferring and Wistar rats

Background: Low packing density of glial cells, possibly astrocytes, has been described in the prefrontal cortex and hippocampus of "uncomplicated" alcoholics. Astrocytes perform crucial support functions in the processing of neurotransmitters and transfer of energy substrates from blood to cortical neurons. It is still unknown whether attrition in the numbers of astrocytes is only a consequence of prolonged alcohol abuse or also predates the exposure to alcohol in subjects at risk for alcohol dependence. Methods: We used alcohol-preferring (P) rats exposed ad libitum for 2 or 6 months to either water only or 10% ethanol and alcohol-nonpreferring (NP) rats and nonselected Wistar rats exposed only to water for 2 months. Sections through the rat frontal cortex were immunostained for glial fibrillary acidic protein (GFAP), a specific marker of astrocytes. The packing density of GFAP-immunoreactive (IR) astrocytes and the area fraction of GFAP immuncreactivity were measured in the prelimbic cortex (PLC) using the dissector probe and analysis of binary images of GFAP immunostaining, respectively. Results: The packing density of GFAP-IR astrocytes was significantly lower in both alcohol-naive and alcohol-exposed P rats than in NP rats or Wistar rats. The area fraction of GFAP immunoreactivity was significantly lower in the alcohol-exposed P rats than in NP rats, Wistar rats, and alcohol-naive P rats. Conclusion: These results suggest that low density of GFAP-IR astrocytes in the PLC of P rats predates the exposure to alcohol and might be a factor contributing to the increased risk for alcohol dependence, In addition, prolonged free-choice alcohol drinking may reduce the extent of GFAP-IR processes in the PLC of P rats.