Capsaicin produces antidepressant-like effects in the forced swimming test and enhances the response of a sub-effective dose of amitriptyline in rats

Physiol Behav. 2018 Oct 15;195:158-166. doi: 10.1016/j.physbeh.2018.08.006. Epub 2018 Aug 20.


Transient receptor potential vanilloid 1 (TRPV1) channels have been implicated in depression and anxiety. The aim of this study was to evaluate the antidepressant-like properties of the TRPV1 agonist capsaicin using the forced swimming test (FST) in rats. Capsaicin (0.001-0.25 mg/kg, i.p.) produced a reduction of immobility in the FST. A maximally effective dose of the tricyclic antidepressant amitriptyline (12 mg/kg) reduced immobility as well. Notably, doses of capsaicin (1 pg/kg, 1 ng/kg, and 0.001 mg/kg) that were ineffective when applied alone produced a significant decrease in immobility when combined with a subthreshold dose of amitriptyline (5 mg/kg). Rats treated with capsaicin (0.01 mg/kg) + amitriptyline (5 mg/kg) displayed less immobility than those treated with a maximally effective dose of amitriptyline. The non-pungent TRPV1 channel agonist palvanil (0.05-0.1 mg/kg, i.p.) also decreased immobility in the FST. Capsaicin (0.05 mg/kg) did not affect general locomotion in the open field test, nor performance in the elevated plus maze, or skeletal muscle contraction strength measured in vitro after the FST (at 0.25 mg/kg). Altogether, our results imply that low doses of capsaicin produce antidepressant-like effects, and enhance the effect of a subthreshold dose of amitriptyline in the FST.

Keywords: Amitriptyline; Capsaicin; Depression; Forced swimming test; Palvanil; TRPV1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amitriptyline / pharmacology*
  • Animals
  • Antidepressive Agents / pharmacology*
  • Anxiety
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology*
  • Depressive Disorder / drug therapy*
  • Dose-Response Relationship, Drug
  • Male
  • Muscle Contraction / drug effects
  • Random Allocation
  • Rats, Wistar
  • Swimming
  • TRPV Cation Channels / agonists


  • Antidepressive Agents
  • N-palmitoyl-vanillamide
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Amitriptyline
  • Capsaicin