title: Influence of neonatal tactile stimulation on amphetamine preference in young rats: parameters of addiction and oxidative stress.
abstract: This study investigated the influence of neonatal handling on amphetamine-induced conditioned place preference (CPP), as well as the consequent anxiety-like symptoms and oxidative status related to drug abstinence in young rats. Male pups were exposed to tactile stimulation (TS) or neonatal isolation (NI) for 10 min every day from postnatal day one (PND1) to PND21. After being weaned (PND22), pups were separated by handling type until PND40, when treatment with amphetamine (AMPH-4 mg/kg/mL ip, for 8 days) or vehicle (NaCl 0.9% ip, 1 mL/Kg) in CPP started. AMPH-conditioning evoked drug-preference (in 24h and 96 h) and abstinence symptoms in unhandled (UH) animals, followed by oxidative damage in the cortex, hippocampus and striatum. TS showed beneficial influence, as observed by the decreased drug-preference (24 and 96 h) in relation to UH and NI, showing no abstinence symptoms in this last period, as observed by the reduced anxiety-like symptoms. The oxidative status indicated a protective influence of TS on brain tissues: lower lipid peroxidation (LP) and reduced protein carbonylation (PC) in the cortex, hippocampus and striatum. Furthermore, TS also increased antioxidant defenses in brain tissues and blood: i) increased plasma levels of vitamin C; ii) increased activity of catalase (CAT) and iii) higher levels of glutathione (GSH) in red blood cells (RBC). Moreover, there were positive correlations of AMPH-CPP with PC and LP levels in all the brain areas assessed. In summary, TS modifies AMPH-preference in the CPP paradigm, reducing drug abstinence behaviors, and stimulating the antioxidant defense system, thus protecting the brain areas closely related to addiction in young rats. Studies about TS and addiction in animal models should be extended to the molecular level.
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Caren T D
authors.initials: CT
authors.lastname: Antoniazzi
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Nardeli
authors.initials: N
authors.lastname: Boufleur
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Geisa
authors.initials: G
authors.lastname: Dolci
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Karine
authors.initials: K
authors.lastname: Roversi
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Fábio
authors.initials: F
authors.lastname: Kuhn
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Camila S
authors.initials: CS
authors.lastname: Pase
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Verônica T
authors.initials: VT
authors.lastname: Dias
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Katiane
authors.initials: K
authors.lastname: Roversi
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Barcelos
authors.affiliation: Universidade Federal da Fronteira Sul, Realeza, PR, Brazil.
authors.forename: Dalila M
authors.initials: DM
authors.lastname: Benvegnú
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil. Electronic address: mariliseeb@yahoo.com.br.
authors.forename: Marilise Escobar
authors.initials: ME
authors.lastname: Bürger
mesh_terms: D000662:Amphetamines / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn; D016739:Behavior, Addictive; D003214:Conditioning, Classical; D005260:Female; D008297:Male; D018782:Maze Learning; D018384:Oxidative Stress; D010812:Physical Stimulation; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014110:Touch
chemical_list: D000662:Amphetamines
keywords: Abstinence; Amphetamine; Conditioned place preference; Oxidative stress; Tactile stimulation