Putative Anti-Immobility Action of Acute Insulin Is Attributable to an Increase in Locomotor Activity in Healthy Wistar Rats

Background/Aims: Anti-immobility actions of insulin in diabetic rats that are subjected to the forced swim test (FST) have been reported. In this test, low doses of antidepressants exert actions after long-term treatment, without affecting locomotor activity in healthy rats. Few studies have compared acute and chronic actions of insulin with antidepressants in healthy rats. Methods: We hypothesized that if insulin exerts a true anti-immobility action, then its effects must be comparable to fluoxetine in both a 1-day treatment regimen and a 21-day treatment regimen in healthy, gonadally intact female Wistar rats. Results: The results showed that low levels of glycemia were produced by all treatments, including fluoxetine, and glycemia was lower in proestrus-estrus than in diestrus-metestrus. None of the treatments or regimens produced actions on indicators of anxiety in the elevated plus maze. Insulin in the 1-day regimen increased the number of crossings and rearings in the open field test and caused a low cumulative immobility time in the FST. These actions disappeared in the 21-day regimen. Compared with the other treatments, fluoxetine treatment alone or combined with insulin produced a longer latency to the first period of immobility and a shorter immobility time in the chronic regimen in the FST, without affecting locomotor activity, and more pronounced actions were observed in proestrus-estrus (i.e., a true anti-immobility effect). Conclusion: These results indicate that insulin does not produce a true antidepressant action in healthy rats. The purported antidepressant effects that were observed were instead attributable to an increase in locomotor activity only in the 1-day regimen.