Ketamine and crocin exposure modulate anxiety, depression, memory, and pain processes in adolescent female Wistar rats

Behav Pharmacol. 2025 Dec 1;36(8):596-605. doi: 10.1097/FBP.0000000000000859. Epub 2025 Nov 5.

Abstract

Ketamine, a noncompetitive N-methyl- d -aspartate receptor antagonist, and crocin, the bioactive components of Crocus sativus L. , affect anxiety, depression, memory, and pain processes. It has not yet been clarified that crocin can potentiate the analgesic and antidepressant effects of ketamine, as well as attenuate the anxiogenic and amnesic impacts of ketamine in adolescent rodents. This study was designed to explain this issue in adolescent female Wistar rats. For this aim, elevated plus-maze, forced swim test, step-through, and tail-flick tests were utilized. The results indicated that the adolescent female Wistar rats' body weight increased across 10 days of drug treatment, but it did not differ between the groups. Pretreatment with ketamine [20 mg/kg, intraperitoneally (i.p.)] induced anxiogenic- and antidepressant-related behaviors, as well as amnesic and analgesic impacts in adolescent female Wistar rats. Furthermore, alone injection of crocin (30 mg/kg, i.p.) exerted an antidepressant-related behavior. When ketamine (20 mg/kg, i.p.) and crocin (30 mg/kg, i.p.) were coinjected, crocin could potentiate the analgesic and antidepressant effects of ketamine, as well as attenuate the anxiogenic and amnesic properties of ketamine in adolescent female Wistar rats. These results suggested that crocin causes a modulatory effect on ketamine's anxiogenic- and antidepressant-related behaviors, as well as amnesic and analgesic effects in adolescent female Wistar rats.

Keywords: anxiety; crocin; depression; ketamine; memory; pain; rat.

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Antidepressive Agents / pharmacology
  • Anxiety / drug therapy
  • Behavior, Animal / drug effects
  • Carotenoids* / administration & dosage
  • Carotenoids* / pharmacology
  • Crocus / chemistry
  • Depression / drug therapy
  • Female
  • Ketamine* / pharmacology
  • Maze Learning / drug effects
  • Memory / drug effects
  • Pain / drug therapy
  • Rats
  • Rats, Wistar

Substances

  • Ketamine
  • crocin
  • Carotenoids
  • Antidepressive Agents
  • Analgesics