Diabetes modulates ethanol-induced increase in serotonin release from rat hippocampus: an in vivo microdialysis study.

We examined whether diabetes mellitus (DM) affects the acute ethanol (EtOH)-induced increase in serotonin (5-HT) release from the rat hippocampus, and compared the findings with those obtained from non-DM rats. Hippocampal 5-HT was measured by using in vivo microdialysis. Rats were rendered diabetic by an injection of streptozotocin (STZ). EtOH (0.5, 1.0, or 2.0 g/kg) was intraperitoneally administered or EtOH (25, 50, 100, or 200 mM) was given by intracerebral infusion. EtOH enhanced the extracellular 5-HT levels in both non-DM and DM rats in a dose-dependent manner, especially in non-DM rats, irrespective of administration route. Among three kinds of alcohols tested at same concentration (100 mM), methanol was the most effective in increasing extracellular 5-HT levels of non-DM rats; then, in descending order, EtOH and isopropanol. However, no such tendency was observed in DM rats. Experiments using various antagonists and agonists of 5-HT receptors showed that the functions of 5-HT(1B), 5-HT(2), 5-HT(3), and/or 5-HT(4) receptors in the hippocampus of DM rats differ from those in non-DM rats, suggesting that DM induces dysfunction of central neurotransmitter systems including 5-HT receptors. Acetaldehyde (100 mM), a major metabolite of EtOH, also significantly increased 5-HT release in both non-DM and DM rats. Based on the results that EtOH could increase the 5-HT in non-DM rats than in DM rats while acetaldehyde worked on both rats, it is more likely that alcohol dehydrogenase 1B activity was decreased in DM rats. The present study is the first, to our knowledge, to show that DM modulated the EtOH-induced 5-HT release from the hippocampus in type-1 diabetic rats.