Subchronic treatment with fragments of beta-endorphin prevents electroencephalographic seizures and behavioral alterations induced by centrally administered beta-endorphin in the rabbit.
The effects of some beta-endorphin fragments with neuroleptic-like properties, i.e., tau-endorphin, des-tyr1-tau-endorphin (DT tau E), desenkephalin-tau-endorphin (DE tau E), in comparison with the dopaminergic antagonist haloperidol,- were studied on the EEG and behavioral alterations induced by beta-endorphin in the rabbit. beta-Endorphin administered i.c.v. (5-30 nmol) induced EEG nonconvulsive limbic seizures as well as EEG background and behavioral alterations which were antagonized by naloxone administered i.v. (1-2 mg/kg). Haloperidol, tau-endorphin, DT tau E and DE tau E were unable to prevent beta-endorphin-induced alterations when injected in a single dose i.v. (25-50 micrograms/kg), 15 min before beta-endorphin. Subchronic i.v. administration of DT tau E or DE tau E (25 micrograms/kg/day) for 4 consecutive days prevented completely EEG limbic seizures as well as EEG background and behavioral alterations induced by i.c.v. beta-endorphin injected 15 min after the fourth dose; however, haloperidol (30 micrograms/kg/day) administered with the same schedule as DT tau E or DE tau E was able to prevent only EEG epileptiform and EEG background alterations induced by beta-endorphin. tau-Endorphin administered i.v. for 4 consecutive days (25 micrograms/kg/day) did not consistently influence any of the beta-endorphin effects. Our results show that DT tau E and DE tau E, which are devoid of opioid activity, exert a strong antagonism on ictal seizures as well as on other EEG alterations and behavioral alterations induced by beta-endorphin, and suggest that the antagonism shown by these drugs and by haloperidol on the EEG effects induced by beta-endorphin are exerted at least in part through an indirect action, i.e., an interaction with the dopaminergic system.
Di Giannuario
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Laboratorio di Farmacologia, Istituto Superiore di Sanità, Rome, Italy.
Pieretti
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S
Luzi
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Loizzo
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004569:Electroencephalography; D004723:Endorphins / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D012640:Seizures / Q000517:prevention & control*; D001615:beta-Endorphin / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D004723:Endorphins; D010446:Peptide Fragments; D009270:Naloxone; D001615:beta-Endorphin; C018903:gamma-endorphin, des-Tyr(1)-; C033558:des-enkephalin-gamma-endorphin; D006220:Haloperidol