Effects of intraventricular injection of morphine and beta-endorphin on serotonin release from the spinal cord in rats.
Effects of intraventricular (third ventricle) injection of morphine and beta-endorphin on the release of serotonin (5-HT; 5-hydroxytryptamine) and 5-HIAA (5-hydroxy indolacetic acid) from the spinal cord were studied using urethane anesthetized spinally perfused rats. Intraventricular injection of morphine (25 micrograms) increased the 5-HT level in the perfusate about threefold. The increase of 5-HT release reached at peak between 30 and 60 min after the first injection of morphine. However, the levels of 5-HIAA, a metabolite of 5-HT, was not significantly altered by intraventricular injection of morphine. Furthermore, second intraventricular injection of morphine at the same dose did not increase 5-HT level in the spinal perfusate. In contrast to the results with morphine, beta-endorphin (10 micrograms) administered intraventricularly did not alter the release of 5-HT and 5-HIAA from the spinal cord. In addition, acute antinociceptive tolerance to intraventricular morphine induced by a prior intraventricular injection of morphine was studied in pentobarbital anesthetized rats. Acute tolerance was induced by intraventricular pretreatment with morphine (20 micrograms) for 120 min and the same dose of morphine was injected intraventricularly. The tail-flick test was used as an antinociceptive test. Pretreatment of rats with morphine intraventricularly reduced inhibition of the tail-flick response to intraventricularly injected morphine. The results support our previous hypothesis that beta-endorphin and morphine administered supraspinally activate separate descending systems. Spinopetal serotonergic descending pathway is selectively activated by intraventricularly injected morphine but not beta-endorphin.(ABSTRACT TRUNCATED AT 250 WORDS)
Jung
J S
JS
Sam Chun-Dang Pharmaceutical Co., Seoul, Korea.
Song
D K
DK
Suh
H W
HW
Kim
Y H
YH
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004361:Drug Tolerance; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D001615:beta-Endorphin; D009020:Morphine