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)
Stamidis
H
H
Department of Pharmacology and Toxicology, University of Maryland, Baltimore 21201.
Young
G A
GA
D000818:Animals; D001921:Brain / Q000187:drug effects*; D004361:Drug Tolerance; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D009019:Morphinans / Q000008:administration & dosage / Q000494:pharmacology*; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D007211:Indoles; D009019:Morphinans; D009292:Narcotic Antagonists; D009271:Naltrexone; D009020:Morphine; C055382:naltrindole