Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D₁‐like receptors in neonatal rats

Abstract

BACKGROUND AND PURPOSEDopamine 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 APPROACHSpinal 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 RESULTSDopamine at lower concentrations (<1 mM) depressed sVRP, which is a C fibre-evoked polysynaptic response and believed to reflect nociceptive transmission. At higher concentrations (>1 mM), 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 D1-like but not by D2-like receptor antagonists. SKF83959 and SKF81297, D1-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-HT2A/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 IMPLICATIONSThese results suggested that dopamine at lower concentrations preferentially inhibited sVRP, which is mediated via dopamine D1-like and other unidentified receptors. The dopamine-evoked depression is involved in modulating the spinal functions by the descending dopaminergic pathways. AbbreviationsACSF, artificial cerebrospinal fluid; DRG, dorsal root ganglion; MSR, monosynaptic reflex potential; sVRP, slow ventral root potential IntroductionDopamine is a neurotransmitter in the CNS. Dopamine receptors are classified into five subtypes, referred to as either D1-like (D1 and D5) or D2-like (D2, D3 and D4) receptors (Missale et al., 1998; receptor nomenclature follows Alexander et al. 2011). Dopamine concentration is a key factor in the activation of different receptor subtypes. In the prefrontal cortex, low concentrations of dopamine act on D1-like receptors, while higher concentrations act on D2-like receptors (Zheng et al., 1999;Trantham-Davidson et al., 2004).BJP British Journal of Pharmacology DOI:10.1111DOI:10. /j.1476DOI:10. -5381.2011 788 In the spinal cord, the descending dopaminergic fibre projects from the hypothalamic A11 region (Björklund and Skagerberg, 1979;Skagerberg and Lindvall, 1985;Millan, 2002;Benarroch, 2008), and dopamine can modulate locomotion and nociception (Clemens and Hochman, 2004;Han et al., 2007;Lapointe et al., 2009). In the rat spinal cord, dopamine at concentrations greater than 10 mM activates K + channels, producing hyperpolarization via D2-like receptors, but not D1-like receptors in substantia gelatinosa neurones, which are located in the superficial laminae of the dorsal horn receiving nociceptive inputs (Tamae et al., 2005;Taniguchi...

Endogenously released 5-HT inhibits A and C fiber-evoked synaptic transmission in the rat spinal cord by the facilitation of GABA/glycine and 5-HT release via 5-HT2A and 5-HT3 receptors

“…As previously reported (Kawamoto et al, 2011;Wallis et al, 1993aWallis et al, , 1993bYomono et al, 1992), endogenous 5-HT inhibited MSR in the neonatal rat spinal cord, and the inhibition was reversed by ketanserin. Ketanserin failed to overturn MSR inhibition by bath-applied 5-HT in several previous studies (Crick and Wallis, 1991;Elliott and Wallis, 1992;Manuel et al, 1995), but in our study, MRS inhibition in response to bath-applied 5-HT was also reversed by ketanserin.…”

Contribution of α2A-adrenoceptor subtype to effect of dexmedetomidine and xylazine on spinal synaptic transmission of mice

“…1B, in most experiments, the peak amplitude of the MSR increased with time. Time-dependent increase of MSR is also shown in isolated rat spinal cord (Iwasaki et al, 2013;Kawamoto et al, 2012;Otsuguro et al, 2011). Morphine did not affect the MSR.…”

“…Spinal reflex potentials were recorded in mice using methods established in rats (Otsuguro et al, 2006(Otsuguro et al, , 2011Kawamoto et al, 2012) with some modifications. Briefly, newborn mice were killed by decapitation.…”

Characterization of nociceptive response to chemical, mechanical, and thermal stimuli in adolescent rats with neonatal dopamine depletion

“…The descending noradrenergic and serotonergic pathways to the spinal cord modulate the activity of nociceptive neurons (Jones, 1991;Millan, 2002;Pertovaara, 2006;Saade´and Jabbur, 2008;Heinricher et al, 2009;Wu et al, 2010;Bardin, 2011). Descending dopaminergic controls of nociceptive transmission in the spinal and medullary dorsal horn have recently been reported (Lapirot et al, 2011;Taniguchi et al, 2011;Kawamoto et al, 2012). Using in vivo patch-clamp analysis, Taniguchi et al (2011) reported that dopamine produces direct inhibitory effects on substantia gelatinosa neurons in the spinal cord in response to both noxious and innocuous stimulation of the skin.…”