In the formalin model of tonic nociceptive pain, 8-OH-DPAT produces 5-HT1A receptor-mediated, behaviorally specific analgesia

Abstract The experiments examined antinociceptive and intrinsic behavioral effects induced by the prototypical 5-HT 1A receptor agonist 8-OH-DPAT (8-hydroxy-2-[di- n -propylamino] tetralin) in rats. 8-OH-DPAT (0.01–2.5 mg/kg, subcutaneous (s.c.)) reduced both the paw licking and paw elevation induced by (2.5%) formalin injection into the plantar surface of the right hindpaw; it also produced forepaw treading. All of these effects were completely blocked by pretreatment with WAY 100635 ( N -{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}- N -(2-pyridinyl) cyclohexanecarboxamide trihydrochloride) (0.16 mg/kg, s.c.); prazosin (0.63 mg/kg, s.c.) inhibited forepaw treading, but not 8-OH-DPAT's action on paw elevation and paw licking. Repeated injection of 8-OH-DPAT (0.63 mg/kg, s.c.) twice daily for 4 days, markedly reduced 8-OH-DPAT's ability to produce forepaw treading, but exerted only little and inconsistent effects on its paw licking and paw elevation-inhibiting action. The data indicate that 8-OH-DPAT exerts an analgesic action in the formalin model of tonic nociceptive pain; this action is mediated by 5-HT 1A receptors, and is not confounded by the productive sign (i.e., forepaw treading) of the 5-HT syndrome which 8-OH-DPAT also induces.