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Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex
Stacy A Castner1, Peter S Vosler, Patricia S Goldman-Rakic
1Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA. stacy.castner@yale.edu
Biological Psychiatry
|April 12, 2005
Summary
Amphetamine (AMPH) sensitization in monkeys impairs cognitive tasks, modeling schizophrenia deficits. This study reveals reduced dopamine turnover in key brain areas, supporting AMPH sensitization as a schizophrenia model.
Area of Science:
- Neuroscience
- Primatology
- Psychopharmacology
Background:
- Amphetamine (AMPH) sensitization in monkeys models schizophrenia symptoms.
- The impact on working memory, a core schizophrenia deficit, is unclear.
Purpose of the Study:
- To investigate working memory impairment in AMPH-sensitized monkeys.
- To examine dopamine turnover changes in AMPH-sensitized monkeys.
Main Methods:
- Rhesus monkeys underwent AMPH sensitization over 6 weeks.
- Cognitive tasks (delayed response) and dopamine/metabolite levels were assessed post-sensitization.
- High-performance liquid chromatography with electrochemical detection (HPLC-ECD) was used.
Main Results:
- AMPH-sensitized monkeys showed significant impairment in acquiring cognitive tasks.
- Pretrained monkeys exhibited lasting delayed response deficits post-sensitization.
- Reduced dopamine turnover was observed in the prefrontal cortex and striatum.
Conclusions:
- AMPH sensitization impairs cognitive functions relevant to schizophrenia.
- Reduced dopamine turnover in prefrontal cortex supports this model's relevance.
- This model aids in understanding schizophrenia etiology and cognitive dysfunction treatment.