Differential involvement of 5‐hydroxytryptamine1A (5‐HT1A) receptors in the antinociceptive effects of hyperbaric oxygen (HBO2) and nitrous oxide (N2O) in mice

Abstract

Earlier we reported that a 60‐min exposure to HBO2 induced an antinociceptive response that lasted for up to 90 min following exposure [Zylstra et al., FASEB J 22:711.17, 2008]. Recent studies have reported a sustained antinociceptive effect of a selective, high‐efficacy 5‐HT1A receptor agonist in rodents [Deseure et al., Eur J Pharmacol 568:134, 2007]. To determine whether supraspinal or spinal 5‐HT1A receptors might be involved in HBO2‐ or N2O‐induced antinociception, male NIH Swiss mice (20‐30 g) were exposed to HBO2 (2.5 ATA, 60 min) then removed to room air for 90 min or N2O acutely (11 min). Mice were pretreated with intracerebroventricular (i.c.v.) or intrathecal (i.t.) selective 5HT1A antagonist WAY‐100635 prior to antinociceptive testing using the abdominal constriction test. Results show that both i.c.v. and i.t. pretreatments with WAY‐100635 produced comparable and dose‐related antagonism of the antinociceptive response to HBO2. On the other hand, i.c.v. and i.t. pretreatment with WAY‐100635 had no effect on N2O‐induced antinociception. These results suggest that both supraspinal and spinal 5HT1A receptors are involved in the 90‐min antinociceptive response to a 60‐min exposure to HBO2. However, there does not appear to be a role for 5HT1A receptors in the antinociceptive response to N2O. (Supported in part by NIH Grant GM‐77153, the College of Pharmacy and the Chico Hyperbaric Center.)