ORIGINAL INVESTIGATION Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose Tomáš Páleníček & Marie Balíková & Věra Bubeníková-Valešová & Jiří Horáček Received: 16 April 2007 / Revised: 14 August 2007 / Accepted: 21 August 2007 # Springer-Verlag 2007 Abstract Rationale Mescaline is a nonselective serotonin receptor agonist. It has relatively delayed onset of action and prolonged duration. Mescaline attenuates various behavior- al 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. Keywords Mescaline . Locomotion . Sensorimotor gating . Rats . Pharmacokinetics Introduction Mescaline (3,4,5-trimethoxyphenethylamine) is an active compound of the hallucinogenic cacti peyote (Lophophora williamsii). It has a strong potency to induce altered states of consciousness in humans and produces a variety of symp- toms in animals. Mescaline is a serotonin receptor agonist and shows affinities mainly to 5-HT 1A and 5-HT 2A/B/C serotonin receptors (Nichols 2004; Monte et al. 1997; Harms et al. 2003). The proportion of mescaline agonism on each receptor subtype is less clear, as is the action on dopaminergic and noradrenergic systems (Monte et al. 1997; Spinella 2001; Laing and Siegel 2003; Harms et al. 2003). Due to its low lipid solubility arising from its polar molecular characteristics, mescaline does not pass through the blood–brain barrier well, and therefore, higher doses are needed relative to other hallucinogens to produce a psycho- tropic effect (Spinella 2001; Laing and Siegel 2003). Mescaline is reported to undergo O-demethylation, N- acetylation, and amine oxidation with different enzyme systems (Musacchio and Goldstein 1967; Scheline 1978). However, all of the metabolites are believed to be inactive (Baselt 2002). In humans, 87% of an oral dose is excreted Psychopharmacology DOI 10.1007/s00213-007-0926-5 T. Páleníček (*) : V. Bubeníková-Valešová : J. Horáček Prague Psychiatric Center, Ústavní 91, 181 03 Prague 8, Bohnice, Czech Republic e-mail: palenicek@pcp.lf3.cuni.cz M. Balíková Institute of Forensic Medicine and Toxicology, 1st Medical Faculty, Charles University in Prague, 121 08 Prague 2, Czech Republic