PHARMACO-ONTOGENY AND POSSIBLE MECHANISMS INVOLVED IN MU- AND KAPPA-RECEPTOR MEDIATED ANTI-NOCICEPTION.
Item
-
Title
-
PHARMACO-ONTOGENY AND POSSIBLE MECHANISMS INVOLVED IN MU- AND KAPPA-RECEPTOR MEDIATED ANTI-NOCICEPTION.
-
Identifier
-
AAI8708284
-
identifier
-
8708284
-
Creator
-
GIORDANO, JAMES J.
-
Contributor
-
Gordon A. Barr
-
Date
-
1987
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Psychology, Psychobiology
-
Abstract
-
Both the mu agonist morphine and the kappa agonist ketocyclazocine (KC) produce analgesia in the rat. The goals of this thesis were to characterize the unique properties of mu and kappa receptor-mediated analgesia and address possible mechanisms involved in these systems.;Experiments examining developmental patterns of morphine- and KC-analgesia in tests of thermal and mechanical nociception in the preweanling rat demonstrated differences in ontogeny, stimulus-specificity and somatotopy between mu and kappa opioid receptor systems: In both thermal and mechanical tests, morphine analgesia in rostral body parts developed prior to KC-analgesia; while the development of KC-analgesia preceded morphine effects in caudal regions by several days. Further, morphine was more analgesic in thermal and high intensity mechanical tests than KC.;A working model conceptualizing possible neural mechanisms involved in mu and kappa receptor-mediated analgesia was proposed. In this mode, kappa receptors mediate analgesia segmentally within the spinal cord; mu receptors, located primarily supraspinally within the periaqueductal gray (PAG) exert antinociceptive effects through interaction with descending spinal monoamine pathways. The ontogeny of kappa receptor-mediated analgesia was seen as dependent upon the functional development of kappa sites in the cord, while a critical determinant of mu receptor-mediated analgesia was the maturation of descending monoamine tracts.;As 5-HT has been shown to be involved in the expression of opiate analgesia, effects of neonatal depletion of spinal 5-HT on patterns of morphine- and KC-analgesia were determined. Depletion of spinal 5-HT minimally affected patterns of KC-analgesia in both thermal and mechanical tests. Differential roles of spinal 5-HT in morphine thermal and mechanical analgesia were demonstrated. Depletion of spinal 5-HT attenuated morphine-induced thermal analgesia more effectively than mechanical analgesia. These findings suggest that the raphe-spinal 5-HT system is primarily active in mu receptor-mediated thermal analgesia, and implicate involvement of a non-5-HT brainstem system in mu receptor-mediated mechanical analgesia. The different developmental patterns of morphine analgesia against thermal and mechanical noxious input may reflect separate maturation of these multiple PAG-bulbospinal circuits.;These studies provide further evidence that pain modulation involves activation of subpopulations of spinal and supraspinal opioid receptors as well as several bulbospinal neurotransmitter systems.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
-
Program
-
Psychology
