• Kappa-opioid induced regulation of mu-opioid mediated effects on EEG power spectra and behavior in rats

      Paquette, Nicole Corinne; Young, Gerald A. (1991)
      The regulatory effects of kappa-opioid ligands on mu-opioid induced changes in EEG power spectra and behavior were evaluated in rats receiving various acute and chronic treatments. Rats were implanted with cortical EEG electrodes and i.c.v. and/or intravenous (i.v.) cannulae. EEG spectral parameters were derived from digitized EEG samples with spectral analysis techniques. Pretreatment with intracerebroventricular (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 hr later. I.c.v. injections of morphine (20 {dollar}\mu{dollar}g/rat) produced high-voltage, slow-wave EEG bursts (1-10 Hz). Injections of i.c.v. morphine in rats pretreated with i.c.v. dynorphin (20 {dollar}\mu{dollar}g/rat), morphine (20 {dollar}\mu{dollar}g/rat) or dynorphin/morphine twenty-four hours 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 hr 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. Correlated changes in sensitivity to antagonism of these EEG effects by naloxone were also found. Thus, Dynorphin may act as a possible regulator of certain {dollar}\mu{dollar}-opioid receptor-associated phenomena, such as morphine-induced EEG bursts at a binding site which is nor-BNI insensitive. Chronic administration of morphine, a {dollar}\mu{dollar}-opioid selective agonist, for seven days resulted in tolerance development to EEG bursts and EEG absolute power, but not to latency to onset of slow-wave sleep (SWS). Chronic morphine administration was also associated with increases in the duration of hyperexcitability. Chronic administration of U-50,488H, a selective {dollar}\kappa{dollar}-agonist, was not associated with any changes in the duration of EEG bursts, latency to onset of SWS or duration of sedation. The coadministration of U-50,488H and morphine produced no significant tolerance development to the duration of EEG bursts and latency to onset of sleep, but increased the duration of sedation. Morphine or ethylketocyclazocine (EKC) challenges before and after chronic treatment with either morphine or U-50,488H resulted in greater tolerance development to the duration of EEG bursts and to increases in EEG absolute spectral power compared to the group receiving chronic coadministration. (Abstract shortened with permission of author.)