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 re ceptors at the locus coeruleus (LC), using fentanyl-induced muscular r igidity as our experimental index. Adult, male Sprague-Dawley rats ane sthetized with ketamine (120 mg/kg, i.p., with 24 mgg/kg/h i.v. infusi on supplements) were used. Intravenous injection of fentanyl (100 mu g /kg) consistently promoted a significant increase in the electromyogra phic activity recorded from the sacrococcygeus dorsalis lateralis musc le. This implied muscular rigidity was appreciably and dose-dependentl y antagonized by prior intracerebroventricular (i.c.v.) application of NT (15, 30 or 60 nmol/5 mu l). 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-Trp(11))-NT (300 pmol), but n ot by normal rabbit serum (1:80). These results suggest that NT may in teract with the mu-opioid receptors at the LC, resulting in the suppre ssion of fentanyl-induced muscular rigidity in the rat.