LOSS OF AUTORECEPTOR FUNCTION IN DOPAMINERGIC-NEURONS FROM DOPAMINE D-2 RECEPTOR-DEFICIENT MICE

Dopamine plays a key role in the control of motor and cognitive functi ons 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, Pha rmacological and structural analyses have allowed the division of thes e receptors into two classes: the D-1- and D-2-like receptors.(25) The D-1-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 t egmental area and the substantia nigra, These neurons give rise to fou r dopaminergic pathways: the nigrostriatal, the mesolimbic, the mesoco rtical 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) Ind eed, degeneration of the nigrostriatal pathway leads to Parkinson's di sease in humans.(7) characterized by a strong reduction of released do pamine, Thus, a fine tuning of the firing discharge of dopaminergic ne urons is a key function in the regulation of dopamine mediated activit ies in the central nervous system, Somatodendritic dopaminergic autore ceptors of the D-2-like family are responsible for such a function,(21 ) However, it is still controversial whether this function could be as cribed only to one or more members of this subfamily. (C) 1997 IBRO. P ublished by Elsevier Science Ltd.