Abstract
The effects of continuous subcutaneous infusions of rats for 336 h with vehicle, SKF 38393 (a dopamine D 1 receptor agonist), (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, a dopamine D 2 receptor agonist) or both D 1 and D 2 receptor agonists, on locomotor activity were investigated. Rats were maintained under constant lighting conditions, either continuous dark (dark:dark) or continuous light (light:light), before and during drug treatments in order to determine the influence of free-running circadian rhythms on drug responses. The D 2 receptor agonist initially increased locomotion in rats kept under dark:dark during both subjective night (period of maximum locomotion) and day (period of minimum locomotion), but had no effect in rats maintained in light:light throughout the 336 h of treatment. The motor stimulant effects of the D 2 receptor agonist on rats kept in dark:dark increased during the course of treatment during subjective night (sensitization), but decreased during the rats' subjective day (tolerance). The D 1 receptor agonist, SKF 38393, had no effect on its own regardless of the lighting conditions and the duration of treatment. However, the D 1 receptor agonist interacted synergistically with the D 2 receptor agonist in rats maintained under light:light, depending on the duration of treatment. Synergistic effects were also observed on initiation of treatment in rats dark:dark but only during subjective day. Tolerance to the synergistic effects of the receptor agonists occured as a function of treatment duration, but only during subjective day. The D 1 receptor agonist blocked the effects of the D 2 receptor agonist during the rats' subjective night after 100h of traatment, but not after 25 or 325 h. It is concluded that the motor stimulant effects of a D 2 receptor agonist, behavioural D 1/D 2 dopamine receptor interactions, and the development of sensitization and tolerance to the locomotor effects of a D 2 receptor agonist are determined by endogenous free-running circadian rhythms, lighting conditions and duration of treatment.
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