Antagonization of fentanyl-induced muscular rigidity by neurotensin at the locus coeruleus of the rat

We evaluated the interaction between neurotensin (NT) and μ-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 μg/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 μl). 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 μ-opioid receptors at the LC, resulting in the suppression of fentanyl-induced muscular rigidity in the rat.