The investigation of antidepressant and anxiolytic effects of pregabalin and its mechanisms of action in rats

Agri. 2023 Oct;35(4):236-243. doi: 10.14744/agri.2022.98474.


Objectives: Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and neuropathic pain patients. PGB is often combined with anxiolytics and antidepressants. We aimed to investigate the antidepressant and anxiolytic effects of PGB and compare its effects with those of antidepressant and anxiolytic drugs and their combined use.

Methods: Wistar Albino rats were used, and PGB (5, 10, 20, and 40 mg/kg), amitriptylin (AMT), fluoxetine (FLX), ketamine (KET), and diazepam (DZM), as well as combinations of PGB (20 mg/kg) with AMT, FLX, KET, and DZM, were administered. Elevated plus maze, forced swimming, and locomotor activity tests were performed.

Results: In the elevated plus maze, PGB10, 20, 40, AMT, FLX, and DZM increased open arm time. The PGB20+FLX combination increased compared to PGB20. In forced swimming, PGB doses increased immobility time. AMT, FLX, DZM, and KET decreased compared to control and PGB doses. Other combinations of PGB20 reversed immobility time, except FLX. In locomotor activity, PGB20, AMT, KET, and DZM decreased distance.

Conclusion: PGB had a depressant effect in all doses and a dose-dependently anxiolytic effect. In combinations of PGB with AMT, KET, and DZM, it reversed their antidepressant effects. We assumed FLX could be preferred instead of AMT in patients using PGB. When PGB is used in combination, drug interactions should be considered. These results are also very remarkable in terms of pharmacoeconomics.

MeSH terms

  • Amitriptyline
  • Animals
  • Anti-Anxiety Agents* / pharmacology
  • Anti-Anxiety Agents* / therapeutic use
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Epilepsy*
  • Fluoxetine / pharmacology
  • Humans
  • Ketamine* / pharmacology
  • Pregabalin / pharmacology
  • Pregabalin / therapeutic use
  • Rats
  • Rats, Wistar


  • Anti-Anxiety Agents
  • Pregabalin
  • Antidepressive Agents
  • Fluoxetine
  • Amitriptyline
  • Ketamine