Movement initiation characteristics in young adult rats in relation to the high- and low-affinity agonist states of the striatal D 2 dopamine receptor

Abstract

Changes in the speed of movement initiation as a function of age, brain damage, or rat strain are associated with altered characteristics of nigrostriatal dopamine (DA) neurons and of striatal D 2 DA receptors. In the present study we investigated the relationship between movement initiation (response parameters: percent of successful responses and response latency) and the agonist binding states of the D 2 DA receptor in corpus striatum in 3-month-old Sprague-Dawley rats n = 51). In contrast tot he typical experimental procedure, the variances of the behavioral and receptor binding data were intentionally made as small as possible to provide the most stringent test of putative relationships among variables. Rats were trained to release a lever as rapidly as possible in response to a light/buzzer (CS) combination in order to avoid a mild footshock (UCS). Percent avoidance scores, latencies of the fastest successful trials (successful latencies) and mean latencies for all responses (mean latencies) were collected for 1000-, 500-, 300- and 200 mc CS-UCS intervals. Twenty-four hours following the last behavioral test, animals were euthanized for measurements of the high- and low-affinity binding of DA to D 2 receptors in corpus striatum. The standard errors of the mean for both behavioral and receptor binding parameters were, generally, less than 10%. The tightness of the receptor binding data appeared to be related to a lack of biological variance in the animals rather than to an artifact associated with the behavioral testing procedure, since a parallel experiment indicated that different numbers of behavioral shaping sessions had no effects on striatal D 2 biding characteristics. Linear regression techniques were utilized to predict the behavioral performance from the characteristics of striatal D 2 dopamine receptors in the same animals and vice versa. Percent avoidance at the 300 CS-UCS interval and successful latency at the same CS-UCS interval were predicted significantly from the binding data with 30 and 25% of the total variance accounted for, respectively. Similarly, capacities of the high- and low-affinity agonist binding states of the striatal D 2 dopamine receptor [ R h and R l] were predicted significantly from the reaction time data with 56 and 42% of the variance accounted for, respectively. Canonical correlation analysis was used to compare the ability of the set of behavioral [reaction time] parameters and D 2 dopamine receptor binding parameters to predict a common score. This was done by deriving linear combinations for the two sets of variables, behavioral and receptor, such that the correlation between the two linear combinations was maximized. When the behavioral parameters for the 500-ms CS-UCS interval were used as one set of predictor variables and the K d, B max, R h and R l were used as a second set of predictor variables, the canonical correlation was found to have a value of 0.63, which with 12 degrees of freedom (df) is significant at the 0.008 level. When the amount of protein per assay is added to the set of receptor variables, the cononical correlation increases to 0.68 [and with 15 df yields P < 0.006]. This latter result indicates that about 46% of the variance is shared between the two sets of predictor variables. Taken together, these results indicate that it is possible to account for a significant proportion of the total variance in reaction time behavior in drug-free, young adult rodents from the binding of dopamine to striatal D 2 dopamine receptors.