Mu-delta opioid interactions III: Differential antagonism of DPDPE-induced increases in morphine EEG and EEG power spectra by DALCE and naltrindole

Abstract

In the present study, the effects of DALCE ([ d-Ala 2,Leu 5,Cys 6]enkephalin) and naltrindole on DPDPE ([ d-Pen 2, d-Pen 5]enkephalin)-induced increases in morphine EEG and EEG power spectra were assessed. Adult female Sprague-Dawley rats were implanted with cortical EEG electrodes and permanent indwelling ICV and IV cannulae. Rats were pretreated with ICV DALCE at 15.7 nmol, ICV naltrindole at 20 nmol, or ICV sterile water. Rats were then administered ICV DPDPE at 2.5 nmol or ICV sterile water followed, 10 min later, by IV morphine at 3 mg/kg. Morphine-induced changes in EEG global (1–50 Hz) spectral parameters, the duration of morphine-induced high-voltage EEG bursts, the duration of EEG and behavioral excitation, and the latency to onset of slow-wave sleep were assessed. The DALCE pretreatment significantly decreased morphine-induced total spectral power seen in the DPDPE + morphine group. The DALCE pretreatment reversed the effects of DPDPE on the duration of morphine-induced EEG bursts and the duration of EEG and behavioral excitation. The ICV naltrindole, however, had no significant effect on DPDPE-induced increases in morphine EEG, EEG spectral parameters, and behavior. These data, therefore, suggest that DPDPE may be increasing the effects of morphine on EEG through DALCE-sensitive delta opioid receptors associated within the mu-delta opioid receptor complex.