Potentiation of spinal N-methyl-D-aspartate-mediated nociceptive transmission by cocaine-regulated and amphetamine-regulated transcript peptide in rats.
The present study examined the effects of cocaine-regulated and amphetamine-regulated transcript peptide (CARTp) fragment 55-102, on N-methyl-D-aspartate (NMDA)-mediated nociceptive transmission in vivo and in vitro. In-vivo experiments were conducted in Sprague-Dawley rats to evaluate the effects of CARTp on thermal hyperalgesia induced by NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Intrathecal NMDA (1, 2, 4 nmol) or AMPA (0.5, 1, 2 nmol) dose-dependently decreased the tail-flick latency. Intrathecal CARTp was without effect on the tail-flick latency. Interestingly, it significantly enhanced NMDA-induced, but not AMPA-induced, nociceptive effects. The in-vitro effects of CARTp on NMDA-induced or AMPA-induced depolarizations in substantia gelatinosa neurons were studied in rat spinal cord slices. CARTp (100, 300 nM), which caused no significant change of membrane potentials, increased the amplitude of NMDA-induced depolarizations in substantia gelatinosa neurons with little effect on AMPA-induced depolarizations. The present study demonstrates that exogenously applied CARTp selectively facilitates NMDA receptor-mediated nociceptive transmission.
Hsun Lin
Hsun
H
Department of Physiology, Tzu Chi University, Hualien 970, Taiwan.
Chiu
Hong-Yi
HY
Lai
Chih-Chia
CC
D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010147:Pain Measurement / Q000379:methods; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000661:Amphetamine; D003042:Cocaine