Comparative distributions of dopamine D‐1 and D‐2 receptors in the cerebral cortex of rats, cats, and monkeys
Authors: Richfield Eric K. , Young Anne B. , Penney John B. 
Published: January 2005

The distributions and laminar densities of cerebral cortical dopamine D‐1 and D‐2 receptors were studied in rats, cats, and monkeys. Distributions were determined by using alternate, adjacent tissue sections processed for D‐1 and D‐2 receptor subtypes and compared to an adjacent, nearly adjacent, or similar sections stained for Nissl substance. [3H]‐SCH 23390 and [3H]‐spiroperidol (in the presence of 100 nM mianserin) were used to label the D‐1 and D‐2 receptors, respectively. The regional distribution and laminar density of dopamine receptors were determined by in vitro quantitative autoradiography and video densitometry of selected isocortical and peri‐allocortical regions. Granular (prefrontal, primary somatosensory, and primary visual), agranular (primary motor and anterior cingulate), and limbic (entorhinal and perirhinal) cortices were examined. Where possible, homologous areas among the species were compared.

The D‐1 receptor was present in all regions and laminae of the cerebral cortex of rats, cats, and monkeys. The regional densities for the D‐1 receptor were higher in the cat and monkey than in the rat. The rat D‐1 receptor displayed a relatively homogeneous laminar pattern in most regions except that the deeper laminae (V and VI) contained more receptors than the superficial layers. The cats and monkeys, however, had distinctly heterogeneous laminar patterns in all regions of cortex that varied from one region to another and were quite different from that seen in the rat. The cats and monkeys had highest densities of the D‐1 receptor in layers I and II and lowest densities in layers III and IV, whereas layers V and VI were intermediate. The density of D‐1 receptors was greater than the density of D‐2 receptors in all regions and laminae of cerebral cortex of the cat and monkey and greater in most regions and laminae of the rat cerebral cortex.

The D‐2 receptor was also distributed in all regions of the cerebral cortex of rats, cats, and monkeys. The D‐2 receptor was very homogeneous in its regional distribution and laminar pattern compared to the D‐1 receptor in all 3 species. The D‐2 receptor was denser in the superficial layers (I and II) of the cortex than in the deeper layers in the rats, but more homogeneous in the different laminae of the cat and monkey cerebral cortex. The rat cortical D‐2 receptor exceeded the D‐1 receptor in restricted laminae of selective regions.

Kittens demonstrated low densities of both D‐1 and D‐2 receptors in the cerebral cortex. The kitten D‐1 receptor was more homogeneous in its laminar distribution than in similar regions of the adult cat. The increase in D‐1 receptor density and changes in laminar patterns suggest that portions of the cerebral cortical dopamine system may undergo significant changes during development.

The distribution and density of dopamine receptors in this study agrees well with recent data on the cerebral cortical innervation of the dopamine system in different mammals. The density of dopamine receptors parallels the dopaminergic regional and laminar innervation in rats and monkeys (and presumably cats). Both the degree of innervation and the receptor density are greater in monkeys (and presumably cats) compared to rats. There are some differences in the patterns and degree of matching between dopamine innervation and dopamine receptors, which may reflect differences in the sensitivity or specificity of the different techniques or a true mismatch between them.

These results support and extend the notion that the dopamine system has a more widespread role in cerebral cortical function in all mammals than was previously suspected. The high density, variability in laminar density, and regional differences of the D‐1 receptor in cats and monkeys suggest that the dopamine system, especially the D‐1 receptor, may be more involved in higher cortical processing in certain mammals than was presumed.