Effects of Dextromethorphan on Depressive- and Cognitive-Associated Behaviors: A Sexually Dimorphic Study

We investigated the sexually dimorphic effects of Dextromethorphan (DM) on cognitive and depression-like behaviors as well as on hippocampal histology in rats following acute administration.

Wistar rats of both sexes were treated with 25 or 50 mg/kg of DM for 7 days via intraperitoneal injection. At the end of the administration, behavioral studies were performed on the Tail Suspension Test (TST) for depressive-like behaviors and the Y-maze for cognitive behaviors. The rats’ brains were excised and processed for routine histological analysis. 

Our results showed that DM significantly increased (P<0.05) immobility time in the TST in male rats but not female ones, and decreased percentage alternation (P<0.001) on the Y-maze in both male and female rats. Histological analysis revealed no morphological changes in the hippocampus following DM treatment. 

DM impairs cognitive functions in both male and female rats without histologic defects in the hippocampus. However, the induced depressive-like behaviors following DM administration may be sexually dependent.