Selective effects of pirenperone on analgesia produced by morphine or electrical stimulation at sites in the nucleus raphe magnus and periaqueductal gray

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Abstract
Pirenperone, a new serotonin antagonist with a selective affinity for the 5-HT2 receptor, was administered in conjunction with tests for the antinociceptive effects of morphine sulphate and electrical brain-stimulation at sites in the periaqueductal gray (PAG) and nucleus raphe magnus (NRM). Nociception was assessed by tail-flick latencies in a warm water bath and pirenperone (0.04–0.16 mg/kg) had no effect on baseline scores. When administered prior to morphine, pirenperone (0.16 mg/kg) caused significant attenuation of analgesia induced by morphine. Comparable effects of pirenperone were observed when analgesia was produced by electrical stimulation of the NRM. In contrast, pirenperone had no effect on the analgesic effects of PAG stimulation. This pattern of results suggests that a system involving supraspinal 5-HT2 receptors may modulate some of the antinociceptive effects of morphine and stimulation of the NRM. The differential effects of pirenperone on stimulation-produced analgesia at sites in the NRM and PAG is consistent with separate neural substrates for the analgesia observed from stimulation of these two brain regions.