Research ReportEffect of tipepidine with novel antidepressant-like action on c-fos-like protein expression in rat brain

- Tipepidine increased the number of FLI-positive neurons in the CeA, NAc and VTA.
- Tipepidine induced the unique pattern of an increase in FLI-positive neurons.
- A single injection of tipepidine had an antidepressant effect in an animal model.

We previously reported that tipepidine, a centrally acting non-narcotic antitussive, has an antidepressant-like effect in normal and imipramine treatment-resistant depression model rats. Recently, mapping the induction of c-fos-like immunoreactivity (FLI) in the rat brain showed FLI-positive neurons in several brain areas after acute administration of different classes of antidepressants. Here, the effect of a single injection of an antidepressive dose of tipepidine on FLI was studied in seven areas of the rat brain including the central nucleus of the amygdala (CeA) and the nucleus accumbens (NAc). Desipramine was also used for comparison. Rats were anesthetized and perfused 2 h after injection with tipepidine (20 and 40 mg/kg, i.p.), desipramine (10 mg/kg, i.p.), or saline. Then, immunostaining of FLI-positive neurons in brain slices was performed with conventional methods. A single injection of tipepidine increased FLI-positive neurons in the CeA, similar to preexisting antidepressants, and induced the characteristic pattern of an increase in FLI-positive neurons in six other brain areas including the NAc, an effect that was different from other antidepressants. In addition, a single injection of desipramine (10 mg/kg) or tipepidine (20 mg/kg) decreased the immobility time in the forced swimming test to a similar extent. The results obtained from the previous behavioral study and the current immunohistochemical study suggest that tipepidine may be a novel antidepressant.