Differentiation of dopamine receptor types in the central nervous system of the rat

There is considerable evidence to suggest that dopamine (DA), in addition to its role as a precursor of norepinephrine (NE) and ephinephrine, has important physiological actions in its own right. One physiological action of DA seems to be that of a neurotransmitter in the mammalian brain (Hornykiewicz, 1966). In addition, there is evidence that abnormalities of dopaminergic transmission in the central nervous system (CNS) may be of clinical importance. For example, dopaminergic over activity in the mesolimbic forebrain may be a primary feature in the etiology of schizophrenia (Meltzer and Stahl, 1976). The drugs used to treat schizophrenia act as DA antagonists in the brain (Snyder et al., 1974; Robinson et al., 1979). Drugs such as phenothiazines and butyrophenones have been shown in clinical studies to be effective in treating the fundamental symptoms of psychosis (Snyder et al., 1974). The results of animal experiments indicate that their principal mode of action is blockade of DA receptor sites in the CNS (VanRossum, 1966). However, these neuroleptics are generally nonspecific in their effects upon DA neurons and thus, cause major undesireable side effects. If new drugs could be discovered that were more structurally selective for different DA systems, then, perhaps these undesireable side effects could be eliminated. In order to develop such drugs, a closer look would have to be made at different DA systems in an attempt to demonstrate DA receptors which are topographically distinct and can thus be selectively regulated by both agonistic and antagonistic agents. The demonstration of more than one DA receptor in mammalian CNS is the subject of the research presented in this thesis