Baseline-dependent effects of amphetamine on attention are associated with striatal dopamine metabolism.
Psychostimulants, such as amphetamine, are widely used to treat attentional deficits. In humans, response to dopaminergic medications is complex with improvement often dependent on baseline performance. Our goal was to determine if attention in rats could be improved by low dose amphetamine in a baseline-dependent manner by examining the relationship between task performance, drug response and monoamine levels in corticostriatal tissue. Firstly, rats performed a signal detection task with varying signal durations before administration of saline, 0.1 or 0.25 mg/kg amphetamine. Following 0.1 mg/kg amphetamine, accuracy in poor performing individuals increased to that of high performing rats. Furthermore, baseline accuracy correlated with the magnitude of improvement after amphetamine. Secondly, neurochemical analysis of monoamine content and gene expression levels in the prefrontal cortex (PFC) and dorsal striatum (CPU) was conducted. CPU homovanillic acid and 5-hydroxyindoleacetic acid levels were increased in poor performers with a significant correlation between the expression of the dopamine transporter gene and baseline accuracy. No changes were found in the PFC. These results indicated poor performance was associated with greater response to amphetamine and altered DA and 5-HT neurotransmitter systems in CPU. These results suggest striatal monoamine function may be fundamental to explaining individual differences in psychostimulant response.
Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia.
Karly M
0000-0003-3714-5118
KM
Turner
Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia.
James
J
Peak
Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia. t.burne@uq.edu.au.|Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Richlands, QLD 4077, Australia. t.burne@uq.edu.au.
Thomas H J
TH
Burne
D000661:Amphetamine / Q000378:metabolism*; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001522:Behavior, Animal; D015306:Biogenic Monoamines / Q000032:analysis; D000697:Central Nervous System Stimulants / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D015259:Dopamine Agents / Q000378:metabolism*; D020869:Gene Expression Profiling; D051381:Rats
D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D000661:Amphetamine