Forebrain Dopamine Receptors in Cognitive, Memory and Learning Processes

Neurons that utilize dopamine (DA) as a neurotransmitter have attracted great interest because of their involvement in the behavioral, endocrine and descending control of major brain functions. DA is known to exert its physiological effects on target neurons through D1-like (D1 and D5) and D2-like (D2, D3 and D4) receptor subtypes. To better understand the DA modulation of brain functions, the distribution and cellular localization of D1 and D2 DA receptors in the rat forebrain is reviewed, and their possible role in cognitive aspects of behavior is discussed. In general, DA receptors are differentially expressed and mostly distributed in different target fields of DA neurons. Both D1 and D2 receptor gene products are found in the cerebral cortex, basal ganglia and hippocampal formation, albeit in different cell groups or neuronal subpopulations, whereas D3 receptors are mainly located in limbic regions. In the cortex, mRNA signals are seen in all the areas and cortical layers except layer I. In the striatum, the most intense signal is found in the caudate-putamen, nucleus accumbens and olfactory tubercle where a large number of cells are strongly labeled for D1 and D2. In the globus pallidus only scattered D2 mRNA-containing cells are present. In contrast, no D1 or D2 messages can be seen in the ventral pallidum. In the basal forebrain, mRNA encoding the D1 receptor is detected in the islands of Calleja. The medial and lateral septal nuclei show a low D2 signal. In the amygdaloid nuclear complex, the strongest D1 receptor message is observed in the basomedial and basolateral nuclei. Conversely, the highest density of D2 mRNA-expressing cells is revealed in the central nucleus. Moderately labeled for D1 and D2 cells are scattered throughout the anterior and posterior subdivisions of the bed nucleus of stria terminalis, and within all subfields of the hippocampal formation and dentate granule cell layer. Differential regional and cellular distribution of DA receptors in the forebrain provides anatomical evidence for an area-specific regulation of the DAergic neurotransmission. It can be inferred that DA facilitates learning, memory and cognition processes via activation of both the D1 and D2 receptors. Biomed Rev 2005; 16: 59-75.