Anatomical and affinity state comparisons between dopamine D1 and D2 receptors in the rat central nervous system

Abstract

The anatomical distributions and affinity states of dopamine D1 and D2 receptors were compared in the rat central nervous system using quantitative autoradiography. [3H]SCH23390 and [3H]spiperone (in the presence of 100 nM mianserin) were used to label the D1 and D2 receptors, respectively. The densities of D1 and D2 receptors displayed a positive correlation among 21 brain regions (Pearson correlation coefficient, r = 0.80, P less than 0.001). The affinity states for the D1 and D2 receptors were found to be quite different from each other, and different from the results obtained by others using homogenate preparations. Both the D1 and D2 receptors were best modeled using a two-state model. In the absence of exogenous guanine nucleotides and using the nonselective agonist dopamine as the competitor, the D1 receptor was primarily in a low affinity agonist state (RH = 21 +/- 6%), whereas the D2 receptor was primarily in the high affinity agonist state (RH = 77 +/- 3%). In the presence of 10 microM guanylyl-imidodiphosphate or guanosine-5'-O-(2-thiophosphate) both the D1 and the D2 receptor were completely in a low affinity agonist state (RL = 100%). These affinity states were found both in the nucleus accumbens and olfactory tubercle using dopamine as the competitor and in the striatum using selective D1 or D2 agonists as competitors. Receptor occupancy of the D2 receptor with either an agonist or antagonist did not alter the affinity states of the D1 receptor, and conversely, receptor occupancy of the D1 receptor did not alter the affinity states of the D2 receptor. The correlation between densities of D1 and D2 receptors provides an anatomical framework for evaluating behavioral and electrophysiological evidence of an interaction between the two dopamine receptor subtypes. This interaction does not appear to be due to a sharing or coupling of G-proteins in such a way that binding to one dopamine receptor subtype alters the affinity state of the other receptor subtype. The differences between dopamine receptor distributions described by labeled agonists and antagonists may be due in part to differences in their affinity states. The low proportion of high affinity state D1 receptors may explain some of the difficulties in assigning specific behavioral roles to the D1 receptor.

Dopaminergic signaling in dendritic spines

“…The relatively slow dynamics of reuptake allows DA to invade the extrasynaptic space for a maximum of 12 μm [31,45] (Figure 2C), supplying a sustained, nearly homogenous, DA concentrations in the 10 nM range. This ambient concentration, which primarily acts on the D2 receptors in their high affinity state in the striatum [46], is believed to play an enabling role in movement, cognition, and motivation [47]. In addition to this tonic signaling, most dopaminergic neurons show phasic activation following primary rewards or environmental cues, with latencies of 50-110 ms and durations of < 200 ms.…”

“…As D1-and D2-coupled signaling differs considerably, the dopaminergic control of D1 and D2 diads should also differ. In addition, if D1-and D2-class receptors are proved to reside in the same spines, they would entitle these spines additional advantages: first, it permits the well-documented D1-D2 synergy/antagonism to occur at the level of individual spines; and second, given the different affinities to and activation profiles of different DA receptors by DA [46], these spines could code DA signaling at a range of concentrations. Regardless of the mechanisms, the same background DA tone may set D1-, D2-, and the putative D1/D2-containing spines at distinct biochemical, physiological, and activity states.…”

Cholinergic interneuron characteristics and nicotinic properties in the striatum

“…Evidence indicates that the short form of D 2 (D 2 S) often serves as the presynaptic autoreceptor that inhibits DA release; whereas the long form (D 2 L) is more likely to be found postsynaptically (Khan et al, 1998;Usiello et al, 2000). Both D 1 -like and D 2 -like receptors are widely expressed in the brain with the relative abundance in the order of (Boyson et al, 1986;Richfield et al, 1989;Levey et al, 1993;Missale et al, 1998).…”

A rational design for the selective detection of dopamine using conducting polymers

“…24 The very low concentration of DA in the extracellular fluid 25 provides a huge challenge for the detection of this analyte. The temporal fluctuation of the DA concentration in the human brain has a critical effect on several neurological disorders, such as Harrington's disease and Parkinson's disease.…”