The Antidepressant Activity of a Taurine-Containing Derivative of 4-Phenylpyrrolidone-2 in a Model of Chronic Unpredictable Mild Stress

Int J Mol Sci. 2023 Nov 21;24(23):16564. doi: 10.3390/ijms242316564.

Abstract

This study investigates the therapeutic potential of a new compound, potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (Compound I), in depression. Willner's chronic unpredictable mild stress model of male Wistar rats was used as a depression model. The rats were randomized into four groups, including an intact group, a Compound I group, a Fluoxetine group, and a control group with saline. Behavioral tests, such as the Porsolt forced swim test, hole-board test, elevated plus maze test, and light-dark box, were used to assess the animals' conditions. Our results demonstrated that Compound I effectively reduced the immobilization time of rats in the forced swim test, increased orientation and exploratory behavior, and decreased the latency period of going into the dark compartment compared to the control group. Hippocampal and striatal serotonin concentrations were increased in the Compound I group, and the compound also reduced the level of corticosterone in the blood plasma of rats compared to the intact animals. These results suggest that Compound I has reliable antidepressant activity, comparable to that of the reference antidepressant Fluoxetine.

Keywords: 4-phenylpyrrolidinone-2 derivative; antidepressant activity; chronic unpredictable mild stress; fluoxetine; hormones.

MeSH terms

  • Animals
  • Antidepressive Agents* / pharmacology
  • Antidepressive Agents* / therapeutic use
  • Behavior, Animal
  • Corticosterone
  • Depression / drug therapy
  • Depression / etiology
  • Disease Models, Animal
  • Fluoxetine* / pharmacology
  • Fluoxetine* / therapeutic use
  • Male
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Wistar
  • Stress, Psychological / drug therapy

Substances

  • Fluoxetine
  • 4-phenylpyrrolidone-2
  • Antidepressive Agents
  • Pyrrolidinones
  • Corticosterone