Antagonization of fentanyl-induced muscular rigidity by neurotensin at the locus coeruleus of the rat.
We evaluated the interaction between neurotensin (NT) and mu-opioid receptors at the locus coeruleus (LC), using fentanyl-induced muscular rigidity as our experimental index. Adult, male Sprague-Dawley rats anesthetized with ketamine (120 mg/kg, i.p., with 24 mg/kg/h i.v. infusion supplements) were used. Intravenous injection of fentanyl (100 micrograms/kg) consistently promoted a significant increase in the electromyographic activity recorded from the sacrococcygeus dorsalis lateralis muscle. This implied muscular rigidity was appreciably and dose-dependently antagonized by prior intracerebroventricular (i.c.v.) application of NT (15, 30 or 60 nmol/5 microliter). Microinjection of the tridecapeptide (300 or 600 pmol/100 nl) into the bilateral LC produced similar results. This suppressive effect of NT on fentanyl-induced muscular rigidity was antagonized by simultaneously administered NT antiserum (1:80), or partially blocked by its antagonist, (D-Trp11)-NT (300 pmol), but not by normal rabbit serum (1:80). These results suggest that NT may interact with the mu-opioid receptors at the LC, resulting in the suppression of fentanyl-induced muscular rigidity in the rat.
Institute of Pharmacology, National Yang-Ming Medical College, Veterans General Hospital-Taipei, Taiwan, ROC.
S W
SW
Wang
M Y
MY
Tsou
T Y
TY
Lee
S H
SH
Chan
P W
PW
Lui
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005283:Fentanyl / Q000037:antagonists & inhibitors; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D009127:Muscle Rigidity / Q000188:drug therapy*; D009496:Neurotensin / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009496:Neurotensin; C024309:neurotensin, Trp(11)-; D005283:Fentanyl