Opioid self-administration and rem sleep EEG power spectra

This study was designed to explore the possible existence of temporal electrophysiological changes in the central nervous system in dependent rats that were self-administering morphine, methadone, l-alpha-acetylmethadol (LAAM), nor-LAAM or dinor-LAAM. Adult, female, Sprague-Dawley rats were implanted with chronic cortical and temporalis muscle electrodes and intravenous (i.v.) cannulas for drug administration. Tolerance and physical dependence were induced by automatic hourly intravenous injections of increasing doses of morphine. Rats were then trained to lever press to selfadminister morphine on a fixed ratio 20 schedule of reinforcement. For some of the rats, morphine was then replaced with methadone, l-alpha-acetylmethadol (LAAM), nor-LAAM or dinor-LAAM. At least l week was allowed for the establishment of stabilized self-injection patterns. Samples of the EEG of successive rapid eye movement (REM) sleep episodes which occurred between self-injections were subjected to power spectral analyses using a Nicolet MED-80 system. During self-administration of these narcotic drugs, the first REM sleep episode following an injection had the faster peak EEG frequency. The peak EEG frequencies of the successive REM sleep episodes during an interinjection interval declined in a linear fashion towards the next injection. Differences in the slopes of the linear peak EEG frequency declines of the different narcotic drugs appear to correlate with differences in the pharmacokinetic profiles. These EEG changes are not related to lever pressing activity since analogous EEG frequency changes were seen in physically dependent rats receiving automatic morphine injections. The slowing in peak EEG frequencies may reflect a decline in brain levels of the respective drug leading to changes in the central nervous system that precede “drug-seeking behavior”.