K Kawamoto1, K Otsuguro, M Ishizuka, S Ito. 1. Laboratories of Pharmacology Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Abstract
BACKGROUND AND PURPOSE: Dopamine released from the endings of descending dopaminergic nerve fibres in the spinal cord may be involved in modulating functions such as locomotion and nociception. Here, we examined the effects of dopamine on spinal synaptic transmissions in rats. EXPERIMENTAL APPROACH: Spinal reflex potentials, monosynaptic reflex potential (MSR) and slow ventral root potential (sVRP), were measured in the isolated spinal cord of the neonatal rat. Dopamine release was measured by HPLC. KEY RESULTS: Dopamine at lower concentrations (<1 µM) depressed sVRP, which is a C fibre-evoked polysynaptic response and believed to reflect nociceptive transmission. At higher concentrations (>1 µM), in addition to a potent sVRP depression, dopamine depolarized baseline potential and slightly depressed MSR. Depression of sVRP by dopamine was partially reversed by dopamine D(1) -like but not by D(2) -like receptor antagonists. SKF83959 and SKF81297, D(1) -like receptor agonists, and methamphetamine, an endogenous dopamine releaser, also caused the inhibition of sVRP. Methamphetamine also depressed MSR, which was inhibited by ketanserin, a 5-HT(2A/2C) receptor antagonist. Methamphetamine induced the release of dopamine and 5-HT from spinal cords, indicating that the release of endogenous dopamine and 5-HT depresses sVRP and MSR respectively. CONCLUSION AND IMPLICATIONS: These results suggested that dopamine at lower concentrations preferentially inhibited sVRP, which is mediated via dopamine D(1) -like and other unidentified receptors. The dopamine-evoked depression is involved in modulating the spinal functions by the descending dopaminergic pathways.
BACKGROUND AND PURPOSE:Dopamine released from the endings of descending dopaminergic nerve fibres in the spinal cord may be involved in modulating functions such as locomotion and nociception. Here, we examined the effects of dopamine on spinal synaptic transmissions in rats. EXPERIMENTAL APPROACH: Spinal reflex potentials, monosynaptic reflex potential (MSR) and slow ventral root potential (sVRP), were measured in the isolated spinal cord of the neonatal rat. Dopamine release was measured by HPLC. KEY RESULTS:Dopamine at lower concentrations (<1 µM) depressed sVRP, which is a C fibre-evoked polysynaptic response and believed to reflect nociceptive transmission. At higher concentrations (>1 µM), in addition to a potent sVRP depression, dopamine depolarized baseline potential and slightly depressed MSR. Depression of sVRP by dopamine was partially reversed by dopamine D(1) -like but not by D(2) -like receptor antagonists. SKF83959 and SKF81297, D(1) -like receptor agonists, and methamphetamine, an endogenous dopamine releaser, also caused the inhibition of sVRP. Methamphetamine also depressed MSR, which was inhibited by ketanserin, a 5-HT(2A/2C) receptor antagonist. Methamphetamine induced the release of dopamine and 5-HT from spinal cords, indicating that the release of endogenous dopamine and 5-HT depresses sVRP and MSR respectively. CONCLUSION AND IMPLICATIONS: These results suggested that dopamine at lower concentrations preferentially inhibited sVRP, which is mediated via dopamine D(1) -like and other unidentified receptors. The dopamine-evoked depression is involved in modulating the spinal functions by the descending dopaminergic pathways.
Authors: Jonathan J Milla-Cruz; Elvia Mena-Avila; Jorge R Calvo; Shawn Hochman; Carlos M Villalón; Jorge N Quevedo Journal: Neurosci Lett Date: 2020-07-16 Impact factor: 3.046