Evidence for mu opioid receptor mediation of enkephalin-induced electroencephalographic seizures.

Abstract

The opioid receptor types involved in the mediation of enkephalin-induced electroencephalographic (EEG) seizures were studied in unanesthetized, freely moving rats. Four receptor-selective peptide ligands were evaluated for effectiveness in producing nonconvulsive EEG seizures after i.c.v. administration; these included the mu agonist, [D-Ala2-N-methyl-Phe4-Gly5-ol]enkephalin (DAGO), the mixed mu-delta agonist, [D-Ala2-D-Leu5]enkephalin (DADLE), and the selective delta agonists, [D-Pen2-D-Pen5]enkephalin and [D-Pen2-L-Pen5]enkephalin. Only DAGO and DADLE were found to produce EEG seizures, with DAGO being 9 times more potent than DADLE. DAGO produced a greater number of seizure episodes with a greater overall incidence compared with DADLE, reflecting its potent effect to elicit EEG seizure activity in these rats. Injections of [D-Pen2-D-Pen5]enkephalin or [D-Pen2-L-Pen5]enkephalin, even at the highest doses tested, failed to produce seizure activity. Behaviorally, the DAGO and DADLE EEG seizures were nonconvulsive but were temporally associated with episodic bursts of wet-dog shakes. The enkephalin-induced responses were extremely sensitive to antagonism by naloxone and completely blocked by pretreatment with the irreversible mu antagonist beta-funaltrexamine. The selective delta opioid receptor antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH) was ineffective. The use of the most selective agonists and antagonists for mu and delta opioid receptors suggests that, in rats, enkephalin-induced EEG seizures are mediated exclusively by mu opioid receptors and not by delta opioid systems.

• Authors: F C Tortella, L Robles, H I Mosberg
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 240 Issue 2 Pg. 571-7 (Feb 1987) ISSN: 0022-3565 [Print] United States
• PMID: 3027318 (Publication Type: Journal Article)

Chemical References

• Enkephalins
• Receptors, Opioid
• Receptors, Opioid, delta
• Receptors, Opioid, mu
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
• Naloxone
• Enkephalin, Leucine
• Naltrexone
• Enkephalin, Leucine-2-Alanine
• beta-funaltrexamine
• Enkephalin, D-Penicillamine (2,5)-
• N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine

Topics

• Animals
• Electroencephalography
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
• Enkephalin, D-Penicillamine (2,5)-
• Enkephalin, Leucine (analogs & derivatives, pharmacology)
• Enkephalin, Leucine-2-Alanine
• Enkephalins (pharmacology)
• Male
• Naloxone (pharmacology)
• Naltrexone (analogs & derivatives, pharmacology)
• Rats
• Receptors, Opioid (drug effects)
• Receptors, Opioid, delta
• Receptors, Opioid, mu
• Seizures (chemically induced, physiopathology)