Role of dopamine receptors in the induction and expression of rotational behavior induced by caffeine in 6-hydroxydopamine-lesioned rats

In order to define the role of dopamine receptors in the contralateral rotational behavior induced by caffeine in unilaterally 6-hydroxydopamine-lesioned rats, we evaluated the influence of previous exposure (priming) to dopamine receptor agonists and the effect of dopamine receptor blockade on the rotational behavior induced by caffeine. 6-Hydroxydopamine-lesioned rats received single or repeated administrations of the D1/D2 receptor agonist apomorphine (0.3 mg/kg s.c.) (primed) or vehicle (drug-naive). Three days later all rats received caffeine (30 mg/kg s.c.). Drug-naive and single-primed rats did not rotate in response to caffeine, whereas rats repeatedly primed with apomorphine rotate contralaterally. When apomorphine priming was paired to the environment (hemispherical bowls) where rats received caffeine, rotational behavior was significantly higher than that obtained in rats primed in an unpaired environment (cylinders). Repeated priming with the D2/D3 receptor agonist quinpirole (0.2 mg/kg s.c.) Induced a totally context-dependent contralateral rotation in response to caffeine, while caffeine contralateral rotation was not dependent on the context after repeated priming with the D1 agonist SKF 38393 (3 mg/kg s.c.). Caffeine context-dependent rotational behavior was antagonized by either D1 or D2 receptor antagonists SCH 23390 (0.03 mg/kg s.c.) And eticlopride (0.03 mg/kg s.c.), whereas caffeine context-independent rotation was not antagonized by SCH 23390 or eticlopride. The results show that: 1) caffeine does not induce any contralateral rotation in drug-naive 6-hydroxydopamine-lesioned rats; 2) repeated priming with a dopamine agonist enables caffeine to induce contralateral rotation; this rotation is, however, dependent on the context when D2 receptors are stimulated; 3) caffeine context-dependent contralateral rotation is counteracted by dopamine antagonists, whereas context-independent rotation is not antagonized by dopamine receptor blockade