Activation of spinal D1/D5 receptors induces late-phase LTP of C-fiber-evoked field potentials in rat spinal dorsal horn

Long- term potentiation ( LTP) of C- fiber evoked field potentials in spinal dorsal horn may be relevant to pathological pain. Our previous work has shown that the late phase of the spinal LTP is protein synthesis - dependent. Considerable evidence has accumulated that dopamine D1/ D5 receptors are important for late- phase LTP in hippocampus. In this study, the role of D1/ D5 receptors in LTP of C- fiber - evoked field potentials in spinal dorsal horn was evaluated in urethan- anesthetized Sprague- Dawley rats. We found the following. 1) Spinal application of SKF 38393, a D1/ D5 receptor agonist, induced a slowly developed LTP of C- fiber - evoked field potentials, lasting for > 10 h, and the effect was blocked by the D1/ D5 antagonist SCH 23390, whereas a D2 receptor agonist ( quinpirole) induced depression of C- fiber responses, lasting for 2 h. 2) The potentiation produced by D1/ D5 receptor agonist occluded the late phase but not the early phase of the spinal LTP produced by tetanic stimulation. 3) SCH 23390 selectively depressed the late- phase LTP, when applied 40 min before tetanic stimulation. 4) The D1/ D5 agonist- induced potentiation is blocked by the protein synthesis inhibitor anisomycin. 5) Activation of protein kinase A by spinal application of 8- Br- cAMP also induced spinal LTP, and the action occluded the potentiation induced by the D1/ D5 receptor agonist. These results suggest that the spinal D1/ D5 receptors participate in the protein synthesis - dependent late- phase LTP of C- fiber - evoked field potentials in spinal dorsal horn through the cAMP signaling pathway.