Antidepressant-like effect of 7-nitroindazole in the forced swimming test in rats

Psychopharmacology (Berl). 2000 Mar;149(1):41-4. doi: 10.1007/s002139900316.

Abstract

Rationale: There is some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in central physiological mechanisms. NO is synthesized from L-arginine by nitric oxide synthase (NOS), as a response to activation of N-methyl-D-aspartate (NMDA) receptors by excitatory amino acids. NMDA receptor antagonists also produce antidepressant-like actions in preclinical models.

Objective: In the present study, the involvement of NO in the mechanism of depression was investigated. 7-Nitroindazole (7-NI) (15, 30, 60, 90 mg/kg IP), a selective inhibitor of neuronal NOS was examined.

Methods: The Porsolt forced swimming test (FST) has been used as a test for screening new antidepressant agents.

Results: 7-NI dose-dependently decreased the immobility time in FST, but produced no significant change in locomotor activity in naive rats. Neither L-arginine, nor D-arginine (100 mg/kg) affected the immobility time in the FST or revealed any effect on locomotion. L-Arginine but not D-arginine, given 10 min before 7-NI, reversed the 7-NI-induced effect on immobility time.

Conclusions: Our findings suggest that NO might be an important modulator of depression in rats.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Arginine / pharmacology
  • Dose-Response Relationship, Drug
  • Immobilization
  • Indazoles / pharmacology*
  • Male
  • Motor Activity / drug effects*
  • Rats
  • Rats, Wistar
  • Swimming
  • Time Factors

Substances

  • Antidepressive Agents
  • Indazoles
  • Arginine
  • 7-nitroindazole