The activation of D₂ and D₃ receptor subtypes inhibits pathways mediating primary afferent depolarization (PAD) in the mouse spinal cord

Somatosensory information can be modulated at the spinal cord level by primary afferent depolarization (PAD), known to produce presynaptic inhibition (PSI) by decreasing neurotransmitter release through the activation of presynaptic ionotropic receptors. Descending monoaminergic systems also modulate somatosensory processing. We investigated the role of D₁-like and D₂-like receptors on pathways mediating PAD in the hemisected spinal cord of neonatal mice. We recorded low-threshold evoked dorsal root potentials (DRPs) and population monosynaptic responses as extracellular field potentials (EFPs). We used a paired-pulse conditioning-test protocol to assess homosynaptic and heterosynaptic depression of evoked EFPs to discriminate between dopaminergic effects on afferent synaptic efficacy and/or on pathways mediating PAD, respectively. DA (10 μM) depressed low-threshold evoked DRPs by 43 %, with no effect on EFPs. These depressant effects on DRPs were mimicked by the D₂-like receptor agonist quinpirole (35 %). Moreover, by using selective antagonists at D₂-like receptors (encompassing the D₂, D₃, and D₄ subtypes), we found that the D₂ and D₃ receptor subtypes participate in the quinpirole depressant inhibitory effects of pathways mediating PAD.