Dopamine phenotype and behaviour in animal models: in relation to attention deficit hyperactivity disorder.

The phenotypic expression of behaviour is the outcome of interacting neuronal networks and is modulated by different subcortical systems. In the present paper the role of a major subcortical neurochemical system, dopamine (DA), is reviewed. In particular, knockout (KO) technology has given an overwhelming insight into the effects of specific component of the dopaminergic system. Therefore, the behavioural profile of dopamine transporter (DAT), tyrosine hydroxylase (TH), DA and cAMP-regulated phosphoprotein (DARPP 32), and D1, D2, D3, D4 and D5 dopamine receptors knockouts (and their combination) is reviewed.TH, D1, D2, D4 KO mice exhibit decreased locomotor activity, perhaps due to decreased motivational level. D3 KO and DAT KO mice show an increase in basal and novelty-induced activity respectively. It is possible that the increased dopamine levels in DAT KO mice enhance motivation. These observations support the hyperDA hypothesis in hyperactive phenotypes. Moreover, they suggest that the inhibitory effect of psychostimulant drugs, such as methylphenidate and amphetamines, in Attention Deficit Hyperactivity Disorder may be the outcome of an altered balance between auto- and hetero-receptors. However, since KO technology is hampered by blockade of the target at early stages of development, some alternatives have been proposed, such as inducible mutagenesis and inhibitory small RNAs conveyed to target by viral vectors in adulthood.