Dopamine (DA) acts as a key neurotransmitter in the brain. Numerous studies have shown its regulatory role for motor and limbic functions. However, in the early stages of Parkinson's disease (PD), alterations of executive functions also suggest a role for DA in regulating cognitive functions. Some other diseases, which can also involve DA dysfunction, such as schizophrenia or attention deficit hyperactivity disorder (ADHD) in children, as shown from the ameliorative action of dopaminergic antagonists and agonists, respectively, also show alteration of cognitive functions. Experimental studies showed that selective lesions of the dopaminergic neurons in rats or primates can actually provide cognitive deficits, especially when the mesocorticolimbic component of the dopaminergic systems is altered. Data from the experiments also showed significant alteration in attentional processes, thus raising the question of direct involvement of DA in regulating attention. Since the dopaminergic influence is mainly exerted over the frontal lobe and basal ganglia, it has been suggested that cognitive deficits express alteration in these subcortical brain structures closely linked to cortical areas, more than simple deficit in dopaminergic transmission. This point is still a matter of debate but, undoubtedly, DA acts as a powerful regulator of different aspects of cognitive brain functions. In this respect, normalizing DA transmission will contribute to improve the cognitive deficits not only related to neurologic or psychiatric diseases, but also in normal aging. Ontogenic and phylogenetic analysis of dopaminergic systems can provide evidences for a role of DA in the development of cognitive general capacities. DA can have a trophic action during maturation, which may influence the later cortical specification, particularly of pre-frontal cortical areas. Moreover, the characteristic extension of the dopaminergic cortical innervation in the rostro-caudal direction during the last stages of evolution in mammals can also be related to the appearance of progressively more developed cognitive capacities. Such an extension of cortical DA innervation could be related to increased processing of cortical information through basal ganglia, either during the course of evolution or development. DA has thus to be considered as a key neuroregulator which contributes to behavioral adaptation and to anticipatory processes necessary for preparing voluntary action consequent upon intention. All together, it can be suggested that a correlation exists between DA innervation and expression of cognitive capacities. Altering the dopaminergic transmission could, therefore, contribute to cognitive impairment. (C) 2002 Elsevier Science Ltd. All rights reserved.
