Loss of autoreceptor function in dopaminergic neurons from dopamine D2 receptor deficient mice.

Dopamine plays a key role in the control of motor and cognitive functions through the interaction with membrane receptors. Dopamine elicits its physiological effect by interacting with receptors that belong to the seven transmembrane domain G-protein-coupled receptors family. Pharmacological and structural analyses have allowed the division of these receptors into two classes: the D 1 - and D 2 -like receptors.25 The D,-like subfamily comprises D 1 and D 5 while the D 2 -like is formed by D 2 , D 3 and D 4 . 8 Dopaminergic neurons arise from the ventral tegmental area and the substantia nigra. These neurons give rise to four dopaminergic pathways: the nigrostriatal, the mesolimbic, the mesocortical and tuberoinfundibular pathways. These pathways are involved in the control of movement,7 learning, 10 motivation 4,18 reward 14 and hormone synthesis and release.22 Dysfunction in these pathways leads to neurological, psychiatric and endocrine disorders. 13,19 Indeed, degeneration of the nigrostriatal pathway leads to Parkinson's disease in humans, 7 characterized by a strong reduction of released dopamine. Thus, a fine tuning of the firing discharge of dopaminergic neurons is a key function in the regulation of dopamine mediated activities in the central nervous system. Somatodendritic dopaminergic autoreceptors of the D 2 -like family are responsible for such a function. 21 However, it is still controversial whether this function could be ascribed only to one or more members of this subfamily.