The role of the nucleus raphe pontis and the caudate nucleus in alfentanil rigidity in the rat.
Attempts to eliminate or reduce the rigidity induced with high-dose narcotic anesthesia in the operating room have been only partially successful. Previous investigations of opioid receptor sites mediating this rigidity have implicated two central regions: the nucleus raphe pontis (NRP) within the reticular formation and the caudate nucleus (CN) within the basal ganglia. The present study used systemically administered alfentanil (ALF), a potent, short-acting fentanyl analog, and intracerebrally infused methylnaloxonium (MN), a quaternary derivative of naloxone, to elucidate further the functional role of the NRP and CN in rigidity. ALF (0.5 mg/kg s.c.) produced a reliable model of rigidity, as documented by gastrocnemius electromyography. The onset of this rigidity was within 60 s of ALF administration, with a total duration of approximately 40-50 min. Intracerebroventricular (i.c.v.) injections of 2.0 or 4.0 micrograms of MN 15 min prior to ALF treatment prevented rigidity, while 0.125 or 0.5 microgram had no significant effect on rigidity. MN injected directly into the NRP at doses as low as 0.125 microgram significantly antagonized ALF-induced rigidity, while injections of MN into the caudate nucleus at doses as high as 4.0 micrograms failed to antagonize ALF-induced rigidity. These observations demonstrate that injection of MN into the NRP is at least 16-fold more effective in blocking ALF-induced rigidity than MN injected into the ventricle and, more importantly, at least 32-fold more effective than MN injected into the CN. The results suggest that the NRP may be an important site for the neural control of muscular rigidity associated with high-dose narcotic administration.
D015760:Alfentanil; D000818:Animals; D002389:Catatonia / Q000139:chemically induced; D002421:Caudate Nucleus / Q000187:drug effects*; D004576:Electromyography; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D009127:Muscle Rigidity / Q000139:chemically induced*; D009270:Naloxone / Q000031:analogs & derivatives; D011149:Pons / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D000644:Quaternary Ammonium Compounds; D015760:Alfentanil; D009270:Naloxone; C041269:N-methylnaloxone; D005283:Fentanyl