EFFECTS OF THE PYRIDOINDOLE DERIVATIVE SME1EC2M3 ON BEHAVIOR, NEUROPLASTICITY, AND BIOCHEMICAL MARKERS IN WISTAR KYOTO RATS

Aim: Failure to respond adequately to at least two antidepressant monotherapies with different mechanisms of action represents a major therapeutic challenge in the treatment-resistant form of depression. Pyridoindole derivative SMe1EC2M3 is a promising candidate with potential antidepressant activity comparable to triple reuptake inhibitors.
Method: Male Wistar Kyoto rats (rat model with depression-like phenotype; n = 6–12 per group) were divided into four experimental groups: vehicle, venlafaxine (Alventa®, 150 mg), venlafaxine + zoletil, and SMe1EC2M3. Animals underwent a battery of behavioral tests, including the splash test, tail flick test, and open field test. Basic biochemical parameters were assessed in plasma. Hippocampal levels of the growth factors VEGF and BDNF were determined using ELISA.
Results: No significant changes were observed in general locomotor activity or nociceptive sensitivity. Treatment with SMe1EC2M3 significantly increased the frequency of grooming behavior in the splash test, indicating an improvement in motivational and self-care-related behavior. Hippocampal BDNF expression remained unchanged. In contrast, VEGF levels were significantly elevated in untreated control animals compared with all treatment groups.SMe1EC2M3 treatment improved multiple plasma parameters, including glucose, phosphorus, and albumin levels, toward physiological ranges compared with other experimental groups.
Conclusion: SMe1EC2M3 treatment improved plasma biochemical parameters, indicating a systemic metabolic effect that may contribute to its overall antidepressant-like profile.