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

In the present study, the effects of DALCE ([D-Ala2,Leu5,Cys6]enkephalin) and naltrindole on DPDPE ([D-Pen2,D-Pen5]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.

Interactions between U-50,488H and sigma receptor antagonists: EEG, EEG power spectral and behavioral correlates.

I.v. administration of U-50,488H after i.v. saline pretreatment produced occasional high-voltage EEG slow-wave bursts that were associated with relatively small increases in spectral power in the 2.5-7.5 Hz band as a spectral peak and with behavioral incidents of sedation, ataxia, ptosis, straub tail, hunching of the back, and backing-up. After pretreatment with the sigma antagonists rimcazole and DuPont Merck S-7389-4, U-50,488H administration produced significantly larger increases in absolute EEG spectral power, both over the 1-50 Hz range and in the 2.5-5.0 and 5.0-7.5 Hz bands, than after saline pretreatment; rimcazole pretreatment eliminated U-50,488H-induced incidents of ataxia, ptosis, hunching of the back and backing-up. In summary, effects of U-50,488H on EEG, EEG power spectra and behavior may reflect interactions between kappa opioid and sigma (non-opioid) receptor-effector systems.

Cholecystokinin octapeptide alters morphine-induced effects on EEG power spectra both quantitatively and qualitatively.

In the present study, EEG analysis was used to determine if cholecystokinin octapeptide (CCK-8) has an effect on the EEG spectral profile associated with morphine-induced bursting. Adult female Sprague-Dawley rats were implanted with cortical electrodes and indwelling i.c.v. and i.v. cannulas. On the day of the experiment, each rat received an i.c.v. injection of either H2O or one of four doses of CCK-8: 8.0, 16.0, 32.0 or 64.0 ng. Ten minutes after receiving the i.c.v. injection, each rat received a 10.0 mg/kg dose of morphine by i.v. injection. Neither the i.c.v. injections of H2O nor CCK-8 produced any EEG bursting or behavioral stupor. However, the i.v. injection of morphine produced high-voltage, slow-wave EEG bursts in all rats. Analysis of EEG recorded during bursting showed that both the 32.0 and 64.0 ng doses of CCK-8 increased absolute power associated with morphine-induced bursting, and comparison of the distribution of power across the range of frequency bands between the control (H2O) and the 32.0 ng dose of CCK-8 revealed that CCK-8 caused a significant change in the pattern of distribution of power. Furthermore, significant dose-related differences were found in the global (1-50 Hz) parameters absolute power, mean frequency, mobility, complexity and edge frequency. Significant differences among the five groups were not found in the parameter of peak frequency, or in either latency to slow-wave sleep or duration of morphine-induced bursting. These results demonstrate that CCK-8 caused both quantitative and qualitative changes in the EEG spectral profile associated with morphine-induced bursting.

Mu-delta opioid interactions. II: Beta-FNA inhibits DPDPE-induced increases in morphine EEG and EEG spectral power.

In the present study, the effects of beta-FNA on DPDPE-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 administered ICV beta-FNA at 20 nmol or ICV sterile water. Then 18-24 h later, rats were 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 period of EEG and behavioral excitation, and the latency to onset of slow-wave sleep were statistically analyzed using a one-way analysis of variance. beta-FNA pretreatment significantly decreased morphine-induced total spectral power seen in the DPDPE + morphine group. beta-FNA pretreatment also significantly decreased the duration of morphine-induced EEG bursts, the period of EEG and behavioral excitation, and the latency to onset of slow-wave sleep in the DPDPE + morphine group. These data, therefore, suggest that DPDPE may be increasing the effects of morphine on EEG through delta opioid receptors associated with the mu-delta opioid receptor complex.

Mu-delta opioid interactions. I: The delta peptide, DPDPE, increases morphine-induced EEG and EEG spectral power.

The effects of the selective delta peptide, DPDPE ([2-D-penicillamine,5-D-penicillamine]enkephalin), on morphine-induced 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 sterile water or ICV DPDPE at 1.25, 2.5, or 5.0 nmol, 10 min before receiving IV morphine at 3 mg/kg. The treatments produced high voltage EEG bursts and associated behavioral stupor. The EEG data were further analyzed on a Pathfinder II computer and statistical analysis of EEG spectral parameters was performed by using a one-way ANOVA followed by Turkey's HSD. ICV DPDPE at 2.5 nmol and 5.0 nmol significantly increased EEG absolute global spectral power. Furthermore, ICV DPDPE at 2.5 and 5.0 nmol significantly increased the duration of morphine-induced high voltage EEG bursts. These data further indicate an in vivo interaction between mu and delta opioid receptors.

Naltrindole retards tolerance development to morphine-induced effects on EEG and EEG power spectra.

In the present study, EEG and EEG power spectra were used to assess the effects of naltrindole, a selective delta opioid antagonist, on the development of tolerance to morphine. Adult female Sprague-Dawley rats were implanted with cortical EEG electrodes and permanent indwelling i.c.v. and i.v. cannulas. Twice daily for 7 days, rats were pretreated with either i.c.v. naltrindole (20 nmol) or i.c.v. water, 20 min before i.v. morphine (10 mg/kg) injections. The treatments produced EEG slow-wave bursts and associated behavioral stupor. The amount and duration of these effects decreased less rapidly over the 7 days in the naltrindole-pretreated rats than in the water-pretreated rats. I.c.v. naltrindole pretreatment also prevented significant decreases in latency to onset of slow-wave sleep that were seen in the i.c.v. water-pretreated group. EEG data were further analyzed on a Pathfinder II computer. The development of tolerance was reflected by decreases in the total absolute EEG spectral power (1-50 Hz) over the 7-day period. Rats that were pretreated with i.c.v. naltrindole (20 nmol) did not display a significant decrease in total absolute EEG spectral power by the 7th day, as did the i.c.v. water-pretreated group. Furthermore, significant differences were seen for complexity, mobility, and edge frequency between the two pretreatment groups. A delayed qualitative change in the EEG power spectra was also observed in rats pretreated with i.c.v. naltrindole. On day 1, EEG slow-wave bursts were associated with increases in EEG spectral power over the 1-10 Hz range.(ABSTRACT TRUNCATED AT 250 WORDS)