ABSTRACT
This chapter underscores the difficulties in predicting the overall actions of dopamine (DA) at any given cellular target. This complexity results from the facts that (1) DA can activate five different receptors (DARs) that often act in opposite directions, with the ratio of receptors expression in each cell likely affecting the overall balance of the response; (2) the receptors can homo-or heterodimerize and, consequently, become linked to a variety of G proteins that activate a multitude of signaling pathways; (3) the responses to DA can be amplified, as well as altered, by G protein-associated kinases that also have receptor-independent actions; and (4) the response to receptor activation can change because of time-dependent receptor desensitization. Drugs that target the DAR have many therapeutic applications in terms of brain-associated disorders of motor control, motivation, addictions, and information processing as well as for selected endocrine, cardiovascular, and renal disorders. DAR-knockout mice are viable and fertile but have cognitive and movement dysfunctions as well as certain peripheral deficiencies including hypertension, immune alterations, altered pituitary functions, and mild growth disturbances.
