RATIONALE: Mescaline is a nonselective serotonin receptor agonist. It has relatively delayed onset of action and prolonged duration. Mescaline attenuates various behavioral parameters in rats; however, no information is available about its pharmacokinetics in rats and its relation to the behavioral changes produced by the drug. OBJECTIVES: The present study evaluates the spontaneous locomotor activity and sensorimotor gating in relation to mescaline concentrations in the serum and the brain of rats MATERIALS AND METHODS: Behavioral changes induced by mescaline [10, 20, and 100 mg/kg subcutaneously (s.c.)] were evaluated in an open-field test and testing of the prepulse inhibition of acoustic startle reaction (PPI) 15 and 60 min after drug administration. The time disposition of mescaline 20 mg/kg s.c. in rat serum and brain homogenates was analyzed by gas chromatography-mass spectrometry. RESULTS: Mescaline produced significant inhibitory effects on locomotion in low doses and a biphasic effect with the highest dose. In the PPI test, only when tested 60 min after drug administration, all doses of mescaline disrupted PPI. Besides the experimental protocol, we have observed that approximately 50% of animals receiving 100 mg/kg died within 12 h post-injection. The serum levels of mescaline rapidly increased within 30 min and subsequently quickly decreased; however, the brain concentrations reached a maximum 1 h after administration and remained high for an additional 60 min. CONCLUSIONS: Mescaline had a delayed onset of the main behavioral changes in rats compared to other hallucinogens. Behavioral changes correlated with the pharmacokinetics of the drug.

• MeSH
• Time Factors MeSH
• Habituation, Psychophysiologic drug effects   MeSH
• Hallucinogens pharmacokinetics   toxicity   MeSH
• Inhibition, Psychological MeSH
• Injections, Subcutaneous MeSH
• Rats MeSH
• Mescaline pharmacokinetics   toxicity   MeSH
• Metabolic Clearance Rate physiology   MeSH
• Brain drug effects   metabolism   MeSH
• Orientation drug effects   MeSH
• Gas Chromatography-Mass Spectrometry MeSH
• Motor Activity drug effects   MeSH
• Rats, Wistar MeSH
• Reflex, Startle drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Hallucinogens MeSH
• Mescaline MeSH