A sensitizing regimen of amphetamine that disrupts attentional set-shifting does not disrupt working or long-term memory

• Published in: Behavioural brain research 2008-05, Vol.189 (1), p.170-179
• Main Authors: Featherstone, Robert E., Rizos, Zoe, Kapur, Shitij, Fletcher, Paul J.
• Format: Article
• Language: English
• Subjects: Adaptation, Psychological - drug effects; Adult and adolescent clinical studies; Amphetamine - administration & dosage; Amphetamine sensitization; Analysis of Variance; Animal model; Animals; Attention - drug effects; Attentional set-shifting; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Central Nervous System Stimulants - administration & dosage; Cognition; Conditioning, Operant - drug effects; Delayed non-matching to position; Dopamine; Dose-Response Relationship, Drug; Drug Administration Schedule; Fundamental and applied biological sciences. Psychology; Male; Maze Learning - drug effects; Medical sciences; Memory - classification; Memory - drug effects; Morris water maze; Neuropharmacology; Pharmacology. Drug treatments; Prefrontal Cortex - drug effects; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Rats; Rats, Sprague-Dawley; Schizophrenia; Set (Psychology)
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2007.12.032

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 1 mg/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.