Electroencephalographic assessment of the role of delta receptors in opioid peptide - induced seizures.
DPDPE ([D-Pen2, D-Pen5]-Enkephalin) and DPLPE ([D-Pen2, L-Pen5]-Enkephalin) are conformationally-constrained cyclic analogs of enkephalin with high selectivity for delta opioid receptors. Intracerebroventricular (i.c.v.) administration of each analog acutely produces a complex EEG response in rats characterized by a dose-related increase in spectral power and HVSA (peak frequency of 5.0 Hz) during behavioral stupor, and a theta driving (5.25-8.0 Hz) associated with intense behavioral arousal. These effects were antagonized by high (10 mg/kg), but not low (1.0 mg/kg), doses of naloxone. Both analogs failed to cause EEG or convulsive seizures. In contrast, i.c.v. administration of DADLE ([D-Ala2, D-Leu5]-Enkephalin), an enkephalin analog with activity at both mu and delta binding sites, caused initial nonconvulsive EEG seizures followed by HVSA (3.0 Hz); theta driving was not evident. The incidence of the seizures was dose-related and antagonized by very low doses of naloxone (0.01-1.0 mg/kg). Collectively, the inability of DPDPE and DPLPE to cause seizure activity, and the marked sensitivity of DADLE-induced EEG seizures to naloxone, suggest that delta receptors are not directly responsible for DADLE-induced EEG seizure activity. Furthermore, these data implicate mu opioid receptors as the primary sites responsible for enkephalin-induced seizures.
D000818:Animals; D004569:Electroencephalography; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology
D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-