Differential effects of selective mu-, kappa- and delta-opioid antagonists on electroshock seizure threshold in mice.
The effects of the selective opioid antagonists cyprodime (mu; 1, 3, 10, 30 mg/kg IP), norbinaltorphimine (kappa; 3, 10, 30 mg/kg IP) and naltrindole (delta; 0.3, 1, 3, 10 mg/kg IP) on electroshock seizure threshold in mice were compared with those of the universal opioid antagonist naloxone (0.3, 1, 10 mg/kg IP). Seizure threshold was increased by mu-receptor blocking doses of both cyprodime and naloxone, unaltered by norbinaltorphimine and decreased (in a dose-related manner) by all doses of naltrindole. The effects of naltrindole were similar to those of the established pro-convulsant agent bicuculline (1 mg/kg IP); however, naloxone and cyprodime produced relatively small increases in seizure threshold when compared with phenytoin (doses up to 30 mg/kg IP). The differential effects of mu-, kappa- and delta-receptor antagonists obtained in this study suggest that electroshock seizure threshold in mice may be controlled, at least in part, by a balance between endogenous opioids acting either pro-convulsantly through mu-receptors or anti-convulsantly via delta-receptors.
Jackson
H C
HC
Department of Pharmacology, School of Medical Sciences, University Walk, Bristol, UK.
Nutt
D J
DJ
D000818:Animals; D000927:Anticonvulsants; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009019:Morphinans / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010672:Phenytoin / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000927:Anticonvulsants; D007211:Indoles; D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C058450:cyprodime; D009270:Naloxone; C051844:norbinaltorphimine; D005680:gamma-Aminobutyric Acid; D009271:Naltrexone; D010672:Phenytoin; C055382:naltrindole; D001640:Bicuculline