Yohimbine produces antinociception in the formalin test in rats:: involvement of serotonin1A receptors

Rationale: Previous studies have suggested that the alpha(2)-adrenergic receptor antagonist yohimbine produced antinociceptive effects in the formalin test in rats. However, yohimbine is also an agonist at serotonin (5-HT)(1A) receptors, suggesting the possibility that the antinociceptive effects of yohimbine might be mediated via these receptors. Objective: The purpose of the present studies was to evaluate the potential role of 5-HT1A receptors in mediating the antinociceptive effects of yohimbine. Methods: The antinociceptive effects of yohimbine were evaluated using the formalin test in rats. Results: Yohimbine (2.5-10 mg/kg s.c.) produced dose-related antinociception during both phase I and phase II of the formalin test, and was approximately equipotent and equiefficacious to morphine. The selective 5-HT1A receptor antagonist WAY 100,635 (0.03-3.0 mg/kg s.c.) produced a partial reversal of yohimbine. In comparison, the selective 5-HT1A receptor agonist (+/-)8-hydroxy-dipropylaminotetralin HBr (8OH-DPAT; 1.0 mg/kg s.c.) also produced a dose-related antinociception in the formalin test, although 8OH-DPAT was completely reversed by WAY 100,635 (3.0 mg/kg s.c.). The antinociceptive effects of yohimbine were not antagonized by the 5-HT1B/1D antagonist GR 127935 (1.0 mg/kg and 3.0 mg/kg s.c.), the 5-HT2 antagonist LY53857 (1.0 mg/kg s.c.), or the 5-HT3 antagonist zatosetron (3.0 mg/kg s.c.). Conclusions: The present results demonstrate that yohimbine produces a dose-related antinociception in the formalin test in rats which is mediated in part by the agonistic actions at 5-HTIA receptors.