Electroencephalographic studies on the development of tolerance and cross tolerance to mescaline in the rat

In rats with permanent electrodes, mescaline initially caused immediate EEG desynchronization and behavioral arousal lasting 2-3 hours, after which slow wave sleep and REM sleep reappeared. With continued administration every 6 hours, partial tolerance developed, shown by gradually shorter latencies to sleep onset. Rats tolerant to mescaline were cross-tolerant to LSD and DET but not to amphetamine, even though amphetamine produces similar arousal and EEG effects. These findings support the usefulness of EEG as a quantitative measure of central nervous system function and align with behavioral studies of tolerance and cross-tolerance among hallucinogens.

Study at a glance

Abstract

Recordings of the electroencephalogram (EEG) and the electromyogram (EMG) were collected continuously from rats equipped with permanent cortical and temporalis muscle electrodes. Automatic injections of mescaline were administered through indwelling i.p. cannulas at an initial dose of 30 mg/kg every 6 hrs for the first 2 days. This dose was then increased to 60 mg/kg 6 hr which was given for the duration of the study. The initial injections of the mescaline induced an immediate desynchronization of the EEG and behavioral arousal of the rat, which endured for 2-3 hrs. After this time, slow wave (SW) sleep and rapid eye movement (REM) sleep episodes reappeared, with the return of regular alternations of the sleep-wakefulness cycle. Upon continued administration of the drug, partial tolerance to the arousal effects of mescaline developed, which was reflected by a gradual reduction in the latencies to onset of SW sleep and REM sleep. Rats rendered tolerant to mescaline in this manner were found to be cross tolerant to lysergic acid diethylamide (LSD) and N,N-diethyl-tryptamine (DET). In contrast, cross tolerance did not occur to amphetamine, which exerts similar arousal and EEG desynchronizing effects. These results agree with physiological and behavioral studies of tolerance and cross tolerance among hallucinogens and support the usefulness of the EEG as a quantitative indicator of central nervous system function.