Mitul A. Mehta and Wim J. Riedel Pages 2487 - 2500 ( 14 )
The ascending dopamine system of the mammalian brain has been associated with motor, mnemonic and goaldirected or reward-related behaviour. The most progress in understanding the cortical mechanisms of dopaminergic modulation of function has been made with regards to short-term mnemonic (or working memory) function. Research in experimental animals strongly suggests that stimulation of dopamine D1 receptors in the prefrontal cortex can ameliorate spatial working memory related cognitive deficits, and may even enhance cognitive function in healthy animals. Research in humans has not been able to clearly replicate these findings, partly due to the lack of available agents that can safely be used. Low doses of dopamine D2 receptor agonists such as bromocriptine and pergolide may be able to enhance working memory and executive functions, but these effects may be dependent on the nature of the tasks used and the baseline performance levels of the subjects. Thus, the effects of dopaminergic cognitive enhancers may not be simple, or uniform across subjects. Systematic studies in humans carefully controlling task parameters are needed in order to specify the potential cognitive processes open to enhancement with dopaminergics. However, since the DA receptor subtypes in different brain regions appear to differentially influence similar functions, carefully defining the cognitive processes to be tested against potential therapeutics is an equally important goal. Studies in patients groups using selective dopaminergics are rather restricted, but show promise for designing large-scale clinical trials into the cognitive enhancing properties of potential therapeutic agents that act through the dopamine system.
neurotransmission, Traumatic Brain Injury(TBI), cere-brovascular accidents, catechol-o-methyltransferase(COMT), 6-OHDA, prefrontal cortex
Centre for Neuroimaging Sciences (PO89), Institute of Psychiatry, London SE5 8AF, UK.