Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose
Abstract
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.