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2015 ; 77
(11
): 940-50
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The cognition-enhancing effects of psychostimulants involve direct action in the
prefrontal cortex
#MMPMID25499957
Spencer RC
; Devilbiss DM
; Berridge CW
Biol Psychiatry
2015[Jun]; 77
(11
): 940-50
PMID25499957
show ga
Psychostimulants are highly effective in the treatment of
attention-deficit/hyperactivity disorder. The clinical efficacy of these drugs is
strongly linked to their ability to improve cognition dependent on the prefrontal
cortex (PFC) and extended frontostriatal circuit. The procognitive actions of
psychostimulants are only associated with low doses. Surprisingly, despite nearly
80 years of clinical use, the neurobiology of the procognitive actions of
psychostimulants has only recently been systematically investigated. Findings
from this research unambiguously demonstrate that the cognition-enhancing effects
of psychostimulants involve the preferential elevation of catecholamines in the
PFC and the subsequent activation of norepinephrine ?2 and dopamine D1 receptors.
In contrast, while the striatum is a critical participant in PFC-dependent
cognition, where examined, psychostimulant action within the striatum is not
sufficient to enhance cognition. At doses that moderately exceed the clinical
range, psychostimulants appear to improve PFC-dependent attentional processes at
the expense of other PFC-dependent processes (e.g., working memory, response
inhibition). This differential modulation of PFC-dependent processes across dose
appears to be associated with the differential involvement of noradrenergic ?2
versus ?1 receptors. Collectively, this evidence indicates that at low,
clinically relevant doses, psychostimulants are devoid of the behavioral and
neurochemical actions that define this class of drugs and instead act largely as
cognitive enhancers (improving PFC-dependent function). This information has
potentially important clinical implications as well as relevance for public
health policy regarding the widespread clinical use of psychostimulants and for
the development of novel pharmacologic treatments for
attention-deficit/hyperactivity disorder and other conditions associated with PFC
dysregulation.
|Animals
[MESH]
|Central Nervous System Stimulants/*pharmacology
[MESH]