Pentobarbital attenuates antinociception induced by i.c.v. morphine but not beta-endorphin in the mouse.
The effects of pentobarbital anesthesia (45 mg/kg i.p.) on the inhibition of the tail-flick response induced by beta-endorphin and morphine injected intracerebroventricularly (i.c.v.) and intrathecally (i.t.) were studied in male ICR mice. Pentobarbital anesthesia attenuated the inhibition of the tail-flick response induced by morphine but not beta-endorphin given i.c.v. However, the tail-flick inhibition induced by morphine given i.t. was not attenuated by pentobarbital. beta-Endorphin-(1-27) (3 micrograms) given i.c.v. or naloxone (2 micrograms) given i.t. blocked inhibition of the tail-flick response induced by morphine given i.c.v. only in pentobarbital-anesthetized mice but not in conscious mice. beta-Funaltrexamine (beta-FNA, 2.5 micrograms) given i.c.v. or yohimbine (2 micrograms) and methysergide (2 micrograms) injected i.t. blocked the morphine (i.c.v.)-induced inhibition of the tail-flick response in conscious mice but not in pentobarbital-anesthetized mice. The results indicate that pentobarbital attenuates the morphine-induced inhibition of the tail-flick response by inhibiting descending noradrenergic and serotonergic pathways and uncovers a descending opioid system. The tail-flick inhibition induced by supraspinal morphine is mediated by stimulation of mu-opioid receptors in conscious mice and epsilon-opioid receptors in pentobarbital-anesthetized mice. The epsilon-opioid receptor-mediated descending system activated by supraspinally injected beta-endorphin is not attenuated by pentobarbital anesthesia.
Tseng
L F
LF
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Tang
R R
RR
D000818:Animals; D004347:Drug Interactions; D004743:Enkephalin, Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010424:Pentobarbital / Q000008:administration & dosage*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D001615:beta-Endorphin / Q000008:administration & dosage*
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D004743:Enkephalin, Leucine; D009271:Naltrexone; D001615:beta-Endorphin; C024524:beta-funaltrexamine; D009020:Morphine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D010424:Pentobarbital