title: Anxiety-like effects of meta-chlorophenylpiperazine in paradoxically sleep-deprived mice.
abstract: Chlorophenylpiperazines (CPP) are psychotropic drugs used in nightclub parties and are frequently used in a state of sleep deprivation, a condition which can potentiate the effects of psychoactive drugs. This study aimed to investigate the effects of sleep deprivation and sleep rebound (RB) on anxiety-like measures in mCPP-treated mice using the open field test. We first optimized our procedure by performing dose-effect curves and examining different pretreatment times in naïve male Swiss mice. Subsequently, a separate cohort of mice underwent paradoxical sleep deprivation (PSD) for 24 or 48h. In the last experiment, immediately after the 24h-PSD period, mice received an injection of saline or mCPP, but their general activity was quantified in the open field only after the RB period (24 or 48h). The dose of 5mgmL(-1) of mCPP was the most effective at decreasing rearing behavior, with peak effects 15min after injection. PSD decreased locomotion and rearing behaviors, thereby inhibiting a further impairment induced by mCPP. Plasma concentrations of mCPP were significantly higher in PSD 48h animals compared to the non-PSD control group. Twenty-four hours of RB combined with mCPP administration produced a slight reduction in locomotion. Our results show that mCPP was able to significantly change the behavior of naïve, PSD, and RB mice. When combined with sleep deprivation, there was a higher availability of drug in plasma levels. Taken together, our results suggest that sleep loss can enhance the behavioral effects of the potent psychoactive drug, mCPP, even after a period of rebound sleep.
authors.affiliation: Departamento de Toxicologia e Análises Toxicológicas, Universidade de São Paulo, Brazil.
authors.forename: Daniel Ninello
authors.initials: DN
authors.lastname: Polesel
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Daniela Fukue
authors.initials: DF
authors.lastname: Fukushiro
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, Brazil. Electronic address: ml.andersen12@gmail.com.
authors.forename: Monica Levy
authors.initials: ML
authors.lastname: Andersen
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Karen Tieme
authors.initials: KT
authors.lastname: Nozoe
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Elisa
authors.initials: E
authors.lastname: Mári-Kawamoto
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Luís Paulo
authors.initials: LP
authors.lastname: Saito
authors.affiliation: Departamento de Oftalmologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Fábio Ramos Souza
authors.initials: FR
authors.lastname: Carvalho
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Tathiana Aparecida
authors.initials: TA
authors.lastname: Alvarenga
authors.affiliation: Departamento de Oftalmologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Denise
authors.initials: D
authors.lastname: Freitas
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Tufik
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo, Brazil; Departamento de Psicobiologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Frussa-Filho
authors.affiliation: Centro de Controle de Intoxicações, Universidade Estadual de Campinas, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Lanaro
authors.affiliation: Centro de Controle de Intoxicações, Universidade Estadual de Campinas, Brazil; Laboratório de Química e Toxicologia Forense, Superintendência da Polícia Técnico Científica do Estado de São Paulo, Brazil.
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Costa
authors.affiliation: Departamento de Toxicologia e Análises Toxicológicas, Universidade de São Paulo, Brazil; Departamento de Química Fundamental, Universidade de São Paulo, Brazil.
authors.forename: Marina Franco Maggi
authors.initials: MF
authors.lastname: Tavares
mesh_terms: D000818:Animals; D001007:Anxiety / Q000097:blood / Q000139:chemically induced* / Q000150:complications; D001522:Behavior, Animal / Q000187:drug effects; D015198:Designer Drugs / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D010879:Piperazines / Q000097:blood / Q000494:pharmacology*; D012892:Sleep Deprivation / Q000523:psychology*
chemical_list: D015198:Designer Drugs; D010879:Piperazines; C015068:1-(3-chlorophenyl)piperazine
keywords: CPP; CTRL; Chlorophenylpiperazines; Control; Designer drugs; Intraperitoneal; LC-MS/MS; Liquid chromatography-tandem mass spectrometry; MDMA; MTBE; Meta-chlorophenylpiperazine; Methyl tert-butyl ether; Methylenedioxymethamphetamine; OF; Open field; Orto-chlorophenylpiperazine; PSD; Paradoxical sleep deprivation; QC; Quality control; RB; SRM; Selected reaction monitoring; Sleep deprivation; Sleep rebound; ip; mCPP; oCPP