Yohimbine produces antinociception in the formalin test in rats: involvement of serotonin(1A) receptors

H E Shannon, E A Lutz
Psychopharmacology 2000, 149 (1): 93-7

RATIONALE: Previous studies have suggested that the alpha2-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-HT(1A) 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-HT(1A) receptor antagonist WAY 100,635 (0.03-3.0 mg/kg s.c.) produced a partial reversal of yohimbine. In comparison, the selective 5-HT(1A) 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-HT(1B/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-HT(1A) receptors.

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