title: A sensitizing regimen of amphetamine that disrupts attentional set-shifting does not disrupt working or long-term memory.
abstract: Exposure to an intermittent, escalating dose of amphetamine induces a sensitized state that, both behaviourally and neurochemically, mirrors several features linked to the positive symptoms of schizophrenia. Increasingly it is being realized that cognitive deficits are a core component of schizophrenia; therefore we sought to assess the effects of inducing an amphetamine-sensitized state on memory (working and long-term) and cognitive flexibility, two cognitive domains impaired in schizophrenia. Rats were exposed to a sensitizing regimen of amphetamine (1-5 mg/kg; three times per week for 5 weeks; escalating at 1mg/kg per week) or saline. In experiment 1, animals were tested on an operant delayed non-match to position task (working memory). Experiment 2 used a standard fixed-platform location water maze task (long-term memory), while experiment 3 used a variable-platform location water maze task (long-term memory and working memory). Amphetamine-sensitized animals were not impaired on any of these tasks. In experiment 4, animals were assessed on a strategy selection task in which they were first required to learn to locate a food reward using a particular learning strategy (place or response) then to learn to shift to an alternate learning strategy (response or place). Amphetamine-sensitized animals were not impaired on this task. In the final experiment animals were found to be impaired in performance of the extra-dimensional shift component of an attentional set-shifting task. These results suggest that while amphetamine sensitization does not produce memory impairments similar to those seen in schizophrenia, it does produce strong impairments in set-shifting, suggesting changes in prefrontal function similar to those seen in schizophrenia.
authors.affiliation: Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Rob_Featherstone@camh.net
authors.forename: Robert E
authors.initials: RE
authors.lastname: Featherstone
authors.forename: Zoe
authors.initials: Z
authors.lastname: Rizos
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects; D000661:Amphetamine / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000145:classification / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012718:Set, Psychology
chemical_list: D000697:Central Nervous System Stimulants; D000661:Amphetamine