Antinociceptive effects of intrathecally administered 2-methylserotonin in developing rats

doi:10.1016/S0165-3806(96)00186-1

Developmental Brain Research

Volume 98, Issue 1, January 1997, Pages 142-144

https://doi.org/10.1016/S0165-3806(96)00186-1 Get rights and content

Abstract

The present study examined developmental patterns of antinociception mediated by the spinal 5-HT₃ receptor system in the neonatal rat. Intrathecally administered 2-methylserotonin (25–100 μg) first produced antinociception against formalin-induced acute inflammatory pain at 10 days postnatally, with effect only at the peak dose (100 μg). Intrathecal 2-methylserotonin produced dose-dependent antinociception at 14 and 28 days of age that was attenuated by i.t. pretreatment with the 5-HT₃ receptor antagonist MDL-72222 (10 μg).

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Citation Excerpt :
Interestingly, SR 57227, a 5-HT3 receptor agonist, enhanced the reflex potentials. Similar controversial results were also reported for pain sensation, i.e., 5-HT3 receptors were shown to mediate both pronociceptive (Ali et al., 1996; Oyama et al., 1996) and antinociceptive effects in the spinal cord (Alhaider et al., 1991; Bardin et al., 2000; Giordano, 1997). 5-HT3 receptors are also expressed in the terminals of afferent C fibers in the dorsal horn (Hamon et al., 1989; Kidd et al., 1993; Morales et al., 2001).
Serotonin (5-HT) released from descending fibers plays important roles in spinal functions such as locomotion and nociception. 5-HT_2A and 5-HT₃ receptors are suggested to contribute to spinal antinociception, although their activation also contributes to neuronal excitation. In the neonatal spinal cord, dl-p-chloroamphetamine (pCA), a 5-HT releaser, inhibited both A fiber-evoked monosynaptic reflex potential (MSR) and C fiber-evoked slow ventral root potential (sVRP). The pCA-mediated inhibition was reversed by ketanserin (a 5-HT_2A receptor antagonist) and tropisetron (a 5-HT₃ receptor antagonist). Bath-applied 5-HT also inhibited MSR and sVRP; in this case, the actions of 5-HT were antagonized by ketanserin, but not by tropisetron. The pCA-evoked inhibition of sVRP was reduced by bicuculline (a GABA_A receptor antagonist) and strychnine (a glycine receptor antagonist). Furthermore, ketanserin inhibited the pCA-evoked release of gamma-aminobutyric acid (GABA) and glycine, while tropisetron inhibited the pCA-evoked release of 5-HT. These results suggest that 5-HT released by pCA activates 5-HT_2A receptors, which in turn stimulates the release of GABA/glycine and thereby blocks the spinal nociceptive pathway. 5-HT₃ receptors may be involved in the facilitation of 5-HT release via a positive feedback process.
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Antinociceptive effects of intrathecally administered 2-methylserotonin in developing rats

Abstract

Pain

Neuropharmacology

Eur. J. Pharmacol.

Dev. Brain Res.