THE GABAERGIC SYSTEM OF THE DENTATE GYRUS AFTER WITHDRAWAL FROM CHRONIC ALCOHOL-CONSUMPTION - EFFECTS OF INTRACEREBRAL GRAFTING AND PUTATIVE NEUROPROTECTIVE AGENTS

We have demonstrated that, in the rat hippocampal formation, withdrawa l from chronic alcohol consumption aggravates the ethanol-induced loss of pyramidal neurons and dentate granule cells. We have also shown th at intracerebral grafting and piracetam could have a protective effect in these conditions. In this study we utilized immunocytochemical met hods to investigate whether gamma-aminobutyric acid (GABA)ergic dentat e gyrus cells, which are known to be inhibitory, were also affected by withdrawal from alcohol and, if so, whether putative neuroprotective agents could ameliorate the alterations found. Rats were alcohol-fed f or 6 months and further divided into several groups: (1) alcohol-fed f or an extra 6 months; (2) withdrawn from alcohol for 6 months; (3) wit hdrawn and grafted with newborn rat hippocampal tissue; (4) withdrawn and orally treated with piracetam for 6 months; (5) withdrawn and trea ted systemically with monosialoganglioside GM1 for 6 months; (6) withd rawn and treated with the vehicle used to dissolve the GM1. Control an imals were pair-fed. All animals were killed 12 months after the begin ning of the experiment and processed for GABA immunocytochemistry. GAB A-immunoreactive (IR) neurons in the dentate gyrus were quantified and we found that alcohol-fed animals had a significant reduction in the numerical profile density of GABA-IR neurons in the dentate gyrus as a whole and in the hilus and in the granular layer of the suprapyramida l limb. Withdrawal from alcohol aggravated the GABAergic neuronal loss . Of the treatments used, only piracetam had a striking beneficial eff ect. Data gathered from the present work and from our previous studies indicate that the neuronal loss following chronic alcohol consumption and withdrawal affects both excitatory and inhibitory neurons in the dentate gyrus and that piracetam may have a useful protective role in this condition.