title: Withdrawal from repeated treatment with amphetamine reduces novelty-seeking behavior and enhances environmental habituation in mice.
abstract: Anhedonia associated with a dysphoric state is an important feature of amphetamine withdrawal in humans. We aimed to investigate the effects of amphetamine withdrawal on two motivation-related behaviors in mice: novelty seeking and environmental habituation. Because anxiety can interfere with the behavioral outcome of other tasks, amphetamine-withdrawn mice were also evaluated in the elevated plus maze. Swiss male mice (three months old) were treated with 2.0mg/kg amphetamine for 13 days, every other day, in their home cages (a total of seven injections). Twenty-four hours after withdrawal from drug treatment, mice were tested in a free-choice novelty apparatus containing one familiar and one novel compartment or in the elevated plus maze. Novelty-seeking behavior was assessed by comparing the time spent in the novel compartment vs. the familiar compartment, whereas environmental habituation was concomitantly evaluated by the time-response curve of total locomotion (novel+familiar). Novelty seeking was decreased during amphetamine withdrawal, and this result was not associated with changes in the anxiety-like behavior of mice. Additionally, amphetamine withdrawal enhanced environmental habituation. The concomitant decrease in novelty seeking and the increase in environmental habituation seem to be related to amphetamine withdrawal-induced anhedonia. Thus, the model proposed here could be used as a tool for the study of mechanisms and potential treatment of the anhedonic behavioral consequences of psychostimulant withdrawal.
authors.affiliation: Department of Pharmacology, Federal University of São Paulo, R. Botucatu, 862, Ed. Leal Prado, 1° andar, 04023062, São Paulo, SP, Brazil.
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Fukushiro
authors.forename: Elisa
authors.initials: E
authors.lastname: Mári-Kawamoto
authors.forename: Tatiana C F
authors.initials: TC
authors.lastname: Aramini
authors.forename: Luis P
authors.initials: LP
authors.lastname: Saito
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Costa
authors.forename: Fabiana S
authors.initials: FS
authors.lastname: Josino
authors.forename: Roberto
authors.initials: R
authors.lastname: Frussa-Filho
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage*; D000818:Animals; D004777:Environment; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000523:psychology*
chemical_list: D000661:Amphetamine