'Catatonia' produced by alfentanil is reversed by methylnaloxonium microinjections into the brain.
Alfentanil, a short-acting and powerful analgesic, when injected peripherally to rats (0.5 mg/kg) produced a catatonic state characterized by a rigid akinesia. The present study was designed to explore the neuroanatomical location of the opiate receptors mediating the alfentanil induced catatonia. The catatonic effect of alfentanil was measured using a bar test and depression of locomotor activity in rats tested in photocell cages during an active nocturnal phase of their cycle. Methylnaloxonium HCl (MN), a quaternary derivative of naloxone which does not readily cross the blood-brain barrier, injected into the lateral ventricle significantly reduced the catatonia at doses of 0.125-2.0 micrograms as measured in both the locomotor and bar test. MN perfusion of similar doses directly into the nucleus raphe pontis, but not in the caudate nucleus significantly antagonized the catatonia. These data complement results on alfentanil-induced muscular rigidity (Blasco et al., see companion paper) where EMG indices of rigidity in rats were reversed by microinjections of low doses of MN (0.125 and 0.5 microgram) in the nucleus raphe pontis, but not the caudate nucleus even at a high dose (4.0 micrograms). Together these results suggest that the region of the nucleus raphe pontis is an important neural substrate for opiate-induced muscular rigidity, and that the catatonic state produced by opiates depends on more diffuse opiate receptor activation of which one important component may be the nucleus raphe pontis.
D015760:Alfentanil; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002389:Catatonia / Q000139:chemically induced* / Q000503:physiopathology; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009270:Naloxone / Q000031:analogs & derivatives*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology
D000644:Quaternary Ammonium Compounds; D011957:Receptors, Opioid; D015760:Alfentanil; D009270:Naloxone; C041269:N-methylnaloxone; D005283:Fentanyl