Relationship between regulation of morphine-induced EEG effects and changes in naloxone sensitivity.
The present data indicate that pretreatment with i.c.v. injection of dynorphin, morphine and dynorphin/morphine resulted in quantitative and qualitative changes in EEG power spectra in rats given i.c.v. morphine 24 h later. Correlated changes in sensitivity to antagonism of these EEG effects by naloxone were also found. Rats were implanted with cortical EEG electrodes and i.c.v. and i.v. cannulas. I.c.v. injections of morphine (20 micrograms/rat) produced high-voltage, slow-wave EEG bursts (1-10 Hz) associated with behavioral stupor which lasted about 2 h. Injections of i.c.v. morphine in rats pretreated with i.c.v. dynorphin (20 micrograms/rat), morphine (20 micrograms/rat) or dynorphin/morphine 24 h earlier, produced quantitative increases in absolute EEG spectral power. Injections of i.c.v. morphine in rats pretreated with i.c.v. dynorphin/morphine 24 h earlier, also produced qualitatively different EEG power spectra with a predominant peak in the 4-6 Hz band, similar to the EEG power spectra seen after acute administration of kappa opioids. After 20 min of morphine-induced high voltage EEG bursts, i.v. naloxone was given in sequential doses (0.0025, 0.0125, 0.025, 0.050 mg/kg) every 3 min until the EEG bursts were suppressed for 20 min. Relatively low doses of naloxone suppressed morphine-induced EEG bursts in rats that received i.c.v. H2O/H2O pretreatment. Slightly higher, but significant, doses of naloxone suppressed morphine-induced EEG bursts in rats that received i.c.v. H2O/morphine or dynorphin/H2O pretreatment. Moreover, a 10-fold increase in naloxone dose was needed to suppress EEG bursts in rats that received dynorphin/morphine pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology, University of Maryland, Baltimore 21201.
N C
NC
Paquette
G A
GA
Young
D000818:Animals; D004399:Dynorphins / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D007276:Injections, Intraventricular; D009020:Morphine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004399:Dynorphins; D009020:Morphine