New facts and the concept of physiological regulation of the dopaminergic system function and its disorders.

We present the main results of the study and justification of our opinion on the role of dopamine (DA) retrograde transfer in the cavernous sinus in the regulation of the dopaminergic (DArgic) system activity. We are convinced that under physiological conditions DA - which is continuously retrograde transferred in the cavernous sinus from venous brain effluent to arterial blood supplying the brain and carried by the arterial blood to endothelial cells and perivascular astrocytes of striatal DArgic cell groups - can inhibit dopamine transporter (DAT) expression by a down-regulation mechanism. A new concept of the genesis of DArgic system dysfunction with involvement of DA retrograde transfer in the cavernous sinus is presented. We suggest that future research that aims to explain the genesis of hypo- or hyperfunction of the DArgic system, and DArgic system dysfunction causing Parkinson's disease, attention deficit hyperactivity disorder (ADHD), schizophrenia, and many other psychiatric disorders, must involve two areas: 1) the cavernous sinus, where DA is taken up, and transferred from the venous blood of the cavernous sinus to the arterial blood supplying the brain. To regulate this process pharmacologically, understanding the mechanism and explanation of what determines its course is necessary; 2) brain DArgic structures, whose activity is regulated primarily by the action of DAT. It is essential to clarify whether the expression of the DAT is regulated directly by DA reaching the presynaptic membrane or by any factor secreted by specific perivascular glial cells (astrocytes) under the influence of DA and DA metabolites.