The International Journal of Neuropsychopharmacology

Research Article

Amphetamine-induced memory impairment in a discriminative avoidance task is state-dependent in mice

Leandro Sandaya1 *, Camilla L. Pattia1a2 *, Karina A. Zanina1a2, Sergio Tufika2 and Roberto Frussa-Filhoa1a2 c1

a1 Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil

a2 Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil


In both humans and laboratory animals, the reports of cognitive effects following acute amphetamine (Amph) administration are mixed and depend, for example, on the timing of administration (e.g. before or after task acquisition) and/or on the memory model used. Besides its cognitive effects, Amph produces other important behavioural effects, including alterations in anxiety and general activity, which could modify the subject's internal state, thereby facilitating state-dependent learning. Importantly, state-dependency has been linked to drug dependence in humans. This study evaluates the role of state-dependent learning in Amph-induced memory deficits in mice submitted to a discriminative avoidance task. Mice were given Amph (3 mg/kg) before training and/or before testing in the plus-maze discriminative avoidance task, an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity. Pre-training Amph administration did not affect the ability to learn the discriminative task, but rather induced anxiogenic-like effects and a marked retention deficit in the test session. This memory impairment was completely absent when animals received Amph before both the training and the test sessions. Amph-induced memory impairment of a discriminative avoidance task is state-dependent, such that a response acquired in the ‘Amph state’ cannot be recalled in the normal state. The involvement of anxiety alterations in this ‘Amph state’ is discussed.

(Received August 26 2011)

(Reviewed October 05 2011)

(Revised February 15 2012)

(Accepted March 12 2012)

(Online publication April 23 2012)

Key words

  • Amphetamine;
  • memory;
  • state-dependency


c1 Address for correspondence: R. Frussa-Filho, PhD, Departamento de Farmacologia, UNIFESP, Rua Botucatu, 862, Ed. Leal Prado, 1° andar, 04023062 São Paulo, SP, Brazil. Tel.: (55-11) 5549 4122 Fax: (55-11) 5549 4122 r. 222 Email:


*  These authors contributed equally to this work.

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