Yohimbine produces antinociception in the formalin test in rats: involvement of serotonin(1A) receptors.
BACKGROUND
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.
Shannon
H E
HE
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. H.Shannon@Lilly.Com
Lutz
E A
EA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D005557:Formaldehyde; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D010147:Pain Measurement; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004873:Ergolines; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D005557:Formaldehyde; C090701:GR 127935; D015016:Yohimbine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C064877:zatosetron; C032663:LY 53857