Intrathecal treatment with 6-hydroxydopamine or 5,7-dihydroxytryptamine blocks the antinociception induced by endomorphin-1 and endomorphin-2 given intracerebroventricularly in the mouse.
The involvement of spinopetal noradrenergic and serotonergic systems in antinociception induced by endomorphin-1 (EM-1) and endomorphin-2 (EM-2) given supraspinally or spinally were investigated in male CD-1 mice. Groups of mice were pretreated intrathecally (i.t.) with 6-hydroxydopamine (6-OHDA, 20 microg) or 5,7-dihydroxytryptamine (5,7-DHT, 50 microg) for 3 days before intracerebroventricular (i.c.v.) or i.t. injection of different doses of EM-1 or EM-2, and the tail-flick response was measured for antinociceptive effects. I.t. pretreatment with 6-OHDA for 3 days, which markedly depleted noradrenaline (NA) contents by more than 90%, but not serotonin (5-HT) in the spinal cord, completely abolished the antinociception induced by i.c.v.-administered EM-1 or EM-2. Intrathecal pretreatment with 5,7-DHT for 3 days, which markedly reduced 5-HT contents by more than 92%, but only reduced NA by 14 - 25% in the spinal cord, also markedly attenuated the antinociception induced by i.c.v.-administered EM-1 or EM-2. However, the antinociception induced by i.t.-administered EM-1 or EM-2 was not affected in either 6-OHDA or 5,7-DHT pretreated mice. It is concluded that NA and 5-HT in the spinal cord are involved in the antinociception induced by supraspinally, but not spinally administered EM-1 and EM-2.
Hung
Kuei-chun
KC
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, 53226, USA.
Wu
Hsiang-en
HE
Mizoguchi
Hirokazu
H
Leitermann
Randy
R
Tseng
Leon F
LF
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage*; D000700:Analgesics / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D016627:Oxidopamine / Q000008:administration & dosage*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods
D000700:Analgesics; D009842:Oligopeptides; C105293:endomorphin 1; D015116:5,7-Dihydroxytryptamine; C105294:endomorphin 2; D016627:Oxidopamine