TY - JOUR
T1 - Central and systemic morphine-induced antinociception in mice
T2 - Contribution of descending serotonergic and noradrenergic pathways
AU - Wigdor, S.
AU - Wilcox, G. L.
PY - 1987
Y1 - 1987
N2 - The relative importance of descending serotonergic and noradrenergic pathways to the antinociceptive action of supraspinally and systemically administered morphine sulfate, and to the antinociceptive synergism observed between spinally and supraspinally administered morphine was examined in mice. Morphine administered i.c.v, intrathecally (i.t.), or i.t. + i.c.v. produced a dose-dependent antinociceptive response, as measured by the tail-flick test. The dose-response curve for morphine (i.c.v.) was shifted significantly to the right by equal i.t. doses of methysergide or phentolamine. However, the most pronounced shift to the right was caused by i.t. administration of the selective alpha-2 antagonist yohimbine. Administration of a subantinociceptive dose of morphine (i.t.) along with morphine (i.c.v.) shifted the dose-response curve for morphine (i.c.v.) 6-fold to the left. The resulting dose-response curve for morphine (i.c.v.) was shifted to the right more by phentolamine (i.t.) than by methysergide (i.t.). Similarly, the dose-response curve for morphine (s.c.) was shifted more to the right by phentolamine (i.t.) than by methysergide (i.t.). These results suggest that the descending noradrenergic system, more than the serotonergic system, may be an important component in spinal/supraspinal interactive mechanisms that may mediate the antinociceptive action of systemically administered morphine.
AB - The relative importance of descending serotonergic and noradrenergic pathways to the antinociceptive action of supraspinally and systemically administered morphine sulfate, and to the antinociceptive synergism observed between spinally and supraspinally administered morphine was examined in mice. Morphine administered i.c.v, intrathecally (i.t.), or i.t. + i.c.v. produced a dose-dependent antinociceptive response, as measured by the tail-flick test. The dose-response curve for morphine (i.c.v.) was shifted significantly to the right by equal i.t. doses of methysergide or phentolamine. However, the most pronounced shift to the right was caused by i.t. administration of the selective alpha-2 antagonist yohimbine. Administration of a subantinociceptive dose of morphine (i.t.) along with morphine (i.c.v.) shifted the dose-response curve for morphine (i.c.v.) 6-fold to the left. The resulting dose-response curve for morphine (i.c.v.) was shifted to the right more by phentolamine (i.t.) than by methysergide (i.t.). Similarly, the dose-response curve for morphine (s.c.) was shifted more to the right by phentolamine (i.t.) than by methysergide (i.t.). These results suggest that the descending noradrenergic system, more than the serotonergic system, may be an important component in spinal/supraspinal interactive mechanisms that may mediate the antinociceptive action of systemically administered morphine.
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M3 - Article
C2 - 3612540
AN - SCOPUS:0023176530
SN - 0022-3565
VL - 242
SP - 90
EP - 95
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -