Dynorphin a-(1–13)-morphine interactions: Quantitative and qualitative eeg properties differ in morphine-naive vs. Morphine-tolerant rats

The effects of dynorphin A-(1–13) on cumulative IV morphine-induced EEG and EEG power spectra were studied in naive and morphine-tolerant rats. Adult female Sprague-Dawley rats were implanted with cortical EEG electrodes and permanent indwelling ICV and IV cannulae. In naive rats, dynorphin A-(1–13) quantitatively decreased cumulative IV morphine-induced EEG spectral power as well as qualitatively shifting the relative distribution of spectral power to predominantly faster frequencies. In morphine-tolerant rats, the quantitative and qualitative EEG properties were identical to those in dynorphin A-(1–13) pretreated morphine-naive rats. Thus, dynorphin A-(1–13) pretreatment apparently produced instantaneous acute morphine tolerance. Furthermore, in morphine-tolerant rats, dynorphin A-(1–13) pretreatment quantitatively increased morphine-induced EEG power without qualitatively changing the relative distribution of EEG spectral power. This latter effect may be due to a summation of increased endogenous levels of dynorphin A-(1–13) associated with the development of morphine tolerance and the experimentally administered dynorphin A-(1–13). These results indicate that dynorphin-induced quantitative and qualitative EEG changes of morphine may reflect different underlying processes. That is, quantitative changes may reflect the number of receptors that are activated, while qualitative changes may reflect the nature of the receptor-effector coupling.