Modulation of kainic acid-induced activity in the mouse spinal cord by the amino terminus of substance P: sensitivity to opioid antagonists.
Behavioral sensitization to kainic acid (KA) in the mouse spinal cord appears to be mediated by the amino (N) terminus of substance P (SP), as potentiation of KA is sensitive to capsaicin, mimicked by SP1-7 but not SP5-11, and blocked by SP1-7 antagonists but not by neurokinin antagonists. As naloxone inhibits some effects of SP1-7, this study examines the role of opioid receptors in the mediation of KA-induced sensitization by the N terminus of SP. All drugs were injected i.t. Behavioral sensitization to repeated injections of KA was inhibited by a large (1 micrograms) dose of naloxone. Pretreatment with either naloxonazine or beta-funaltrexamine, mu-selective opioid antagonists, naltrindole, a delta-selective opioid antagonist, or nor-binaltorphimine, a kappa-selective antagonist, failed to alter the development of sensitization to KA, indicating that this phenomenon is not due to mu, delta, or kappa opioid receptors. The ability of 22.5 pmol of SP1-7 to enhance subsequent KA responses was blocked when coadministered with 0.1 micrograms of naloxone. When administered with KA, naloxone not only failed to reverse the potentiative effect of SP1-7, but further enhanced responses to KA for 2 hr after SP1-7. In contrast to pretreatment with SP1-7, coadministration of KA with SP1-7 inhibited the intensity of behaviors. The inhibitory effect of SP1-7 on responses to a single injection of KA was prevented by pretreatment with naltrindole, whereas pretreatment with beta-funaltrexamine blocked the inhibitory effect of SP1-7 on response to KA in a KA-sensitized animal.(ABSTRACT TRUNCATED AT 250 WORDS)
Larson
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Department of Veterinary Pathobiology, University of Minnesota, Saint Paul.
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D000818:Animals; D004357:Drug Synergism; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*
D010446:Peptide Fragments; D011957:Receptors, Opioid; D013373:Substance P; D009270:Naloxone; C036877:substance P (1-7); D007608:Kainic Acid