DOPAMINE-RECEPTORS AND BRAIN-FUNCTION

In the central nervous system (CNS), dopamine is involved in the contr ol of locomotion, cognition, affect and neuroendocrine secretion. Thes e actions of dopamine are mediated by five different receptor subtypes , which are members of the large G-protein coupled receptor superfamil y. The dopamine receptor subtypes are divided into two major subclasse s: the D-1-like and D-2-like receptors, which typically couple to G(s) and G(j) mediated transduction systems. In the CNS, the various recep tor subtypes display specific anatomical distributions, with D-1-like receptors being mainly post-synaptic and D-2-like receptors being both pre- and post-synaptic. D-1 and D-2 dopamine receptors, the most abun dant subtypes in the CNS, appear to be expressed largely in distinct n eurons. Substance P and dynorphin, which are expressed in D-1 receptor -containing neurons, as well as pre-proenkephalin in D-2 receptor-cont aining neurons, have been used as monitors of dopaminergic activity in the CNS. Expression of immediate early genes, in particular fos, has also been found to correlate with dopaminergic transmission. Dopamine released from the hypothalamus controls the synthesis and secretion of prolactin from the anterior pituitary via D-2 dopamine receptors. As yet, none of the dopamine receptor subtypes have been associated with the etiology of psychotic disorders, such as schizophrenia. However, t he recent characterization of D-3 and D-4 receptors which are, interes tingly, expressed in areas of the CNS mediating cognition and affect o r showing increased affinity for certain neuroleptics, have renewed th e interest and hope of finding effective neuroleptics devoid of side e ffects. Finally, the recent production of genetically-derived animals lacking several of these receptor genes should help elucidate which sp ecific physiological paradigms the receptors mediate. Copyright (C) 19 96 Elsevier Science Ltd.