In conscious rabbits, acute intraventricular injection of mescaline at doses of 70, 100, and 150 micrograms per kilogram produced dose-dependent analgesia, measured by electrical stimulation of the tooth pulp. With daily administration of 100 micrograms per kilogram for five days, complete tolerance developed to this antinociceptive effect. Tolerance also developed to the behavioral effects of mescaline after repeated doses, except for a stuporous state, which became more pronounced as treatment continued. Acute mescaline caused EEG arousal; chronic treatment at 100 micrograms per kilogram progressively slowed the return of voltage to original levels. Comparing certain mescaline-induced effects with those of morphine suggests some shared biochemical and neural patterns.
Repeated administration of equipotent doses of morphine (10 mug/kg) and mescaline (100 mug/kg) directly into the brain ventricles of rabbits produces tolerance and cross-tolerance to their pain-blocking effects. Electrical recordings from various brain regions show that partial tolerance also develops to the electroencephalographic changes caused by chronic mescaline treatment. Comparing certain effects of mescaline with those of morphine suggests that the two drugs share some common biochemical and neural mechanisms.
In rabbits, the narcotic antagonist naloxone does not block pain relief (antinociception) caused by 100 micrograms per kilogram of mescaline injected into the brain, but pretreatment with 6-hydroxydopamine (6-OHDA) does prevent this effect. 6-OHDA also prevents the stereotyped behavior that follows central mescaline administration. Because 6-OHDA destroys nerve terminals that contain catecholamines, the findings suggest that catecholamines play a crucial role in the effects produced by the hallucinogen mescaline when given centrally to rabbits.