title: m-Trifluoromethyl-diphenyldiselenide as a pharmacological tool to treat preference symptoms related to AMPH-induced dependence in rats.
abstract: Amphetamine (AMPH) abuse is a world concern and a serious public health problem. Repeated administration of high doses of AMPH induces neuropsychiatric consequences, including addiction, reward and psychosis, whose pharmacological treatment has shown limited effectiveness. The m-trifluoromethyl-diphenyldiselenide [(m-CF3-PhSe)2] has been documented as a promising pharmacological agent in different animal models related to oxidative damage. In this study, we examined the influence of (m-CF3-PhSe)2 on withdrawal following re-exposure to AMPH. Wistar rats received d,l-AMPH or saline in the conditioned place preference (CPP) paradigm for 8days. Then, half of each initial (AMPH or saline) experimental group was treated with (m-CF3-PhSe)2 or vehicle, resulting in four final groups: i) Saline/vehicle; ii) (m-CF3-PhSe)2/saline; iii) AMPH/vehicle; and iv) AMPH/(m-CF3-PhSe)2. After fourteen days of (m-CF3-PhSe)2 treatment, animals were re-exposed to AMPH or vehicle in the CPP paradigm for three more days in order to assess drug re-conditioning and memory/locomotor activity, performed 24h after AMPH re-exposure in the CPP and the Y maze, respectively. Subsequently, ex-vivo assays were carried out in samples of the prefrontal cortex (PFC) of the animals. The (m-CF3-PhSe)2 treatment was able to prevent AMPH-induced re-conditioning symptoms in rats. Behavioral observations in the Y maze task showed no significant changes. AMPH exposure was able to increase 5-HT uptake as well as oxidative damage in the PFC, whereas (m-CF3-PhSe)2 treatment exerted a preventative effect against these alterations. The current findings suggest that (m-CF3-PhSe)2 might be considered a promising therapeutic tool for AMPH-induced addiction.
authors.affiliation: Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria (UFSM), RS, Brazil.
authors.forename: H J
authors.initials: HJ
authors.lastname: Segat
authors.affiliation: Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria (UFSM), RS, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Martini
authors.affiliation: Pós-Graduação em Farmacologia, UFSM, RS, Brazil.
authors.forename: R C S
authors.initials: RCS
authors.lastname: Barcelos
authors.affiliation: Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria (UFSM), RS, Brazil.
authors.forename: C A
authors.initials: CA
authors.lastname: Brüning
authors.affiliation: Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria (UFSM), RS, Brazil. Electronic address: criswn@ufsm.br.
authors.forename: C W
authors.initials: CW
authors.lastname: Nogueira
authors.affiliation: Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria (UFSM), RS, Brazil; Pós-Graduação em Farmacologia, UFSM, RS, Brazil. Electronic address: mariliseeb@yahoo.com.br.
authors.forename: M E
authors.initials: ME
authors.lastname: Burger
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D017646:Organosilicon Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome
chemical_list: D017646:Organosilicon Compounds; C546861:m-trifluoromethyl-diphenyl diselenide; D000661:Amphetamine
keywords: Addiction; Amphetamine; Conditioning; Memory