Multiple receptors for brain dopamine in behavior regulation: Concept of dopamine-e and dopamine-i receptors

Abstract

From current knowledge, it is possible to substantiate the original concept of DAe and DAi receptors including the predicted correlation with the anatomical, histochemical, biochemical and functional features of the distinct neuronal structures, in which they occur; labelling them as neostriatal DAe receptors and mesolimbic DAi receptors appears to be justified. Available data warrant a revision of currently employed behavior and pharmacological tests. When revised in terms of the DAe-DAi concept, assessment of such tests reveals that agents such as (-)NPA, 6, 7ADTN and certain ergot alkaloids like lergotrile, lisuride and, to a less degree, CB-154 are weak DAe agonists and strong DAi antagonists (Table I). The discovery that mesolimbic α-like NE receptors which regulate the DA activity at the level of the mesolimbic DAi, but not neostriatal DAe, receptors show adaptational changes following priming or subacute treatments with apomorphine or haloperidol, opens new perspectives for understanding phenomena such as the development of hypersensitivity to apomorphine etc. Presynaptic DA receptors located within the DA synaps and DA receptors located at DA cell-bodies resemble closely the DAe receptors, although absence of linkage to the enzyme adenylyl cyclase hints at some distinction. It is possible that the distinct classes of DA receptors identified by behavior and pharmacological studies in mice correspond with the DAe and DAi receptors in snails, rats and cats. There is no evidence to suggest that DAe and DAi receptors are directly related to a) so-called DA1 and DA2 receptors which are coupled and uncoupled respectively to the enzyme adenylyl cyclase, or to b) any of the DA-specific binding sites identified with radiolabelled DA agonists or antagonists. Nonetheless, it cannot be excluded that DAe receptors may correspond with DA-specific binding sites identified with tritiated DA and/or haloperidol, and DAi receptors with a particular subclass of DA-specific binding sites identified within certain mesolimbic structures with radiolabelled spiperone. Thus, future work is still required to relate DAe and DAi receptors to particular, molecular entities within the brain.