D1 and D2 dopamine receptor antagonists block caffeine-induced stimulation of locomotor activity in rats

The mechanism of action for the behavioral stimulant effects of caffeine has been extensively studied, but results have been ambiguous and inconsistent. The present study examined the role of dopamine in caffeine-induced stimulation of locomotor activity in rats. d-Amphetamine was also tested for comparison. Locomotor activity of male Sprague-Dawley rats (300-350 g) was measured using two-channel electronic activity monitors. Activity counts were recorded for 30 min following a 30-min pretreatment with either caffeine (3.0-100 mg/kg, IP) or d-amphetamine (0.1-3.0 mg/kg, IP) alone and in combination with the D1 dopamine antagonist SCH23390 (0.01 and 0.003 mg/kg, SC) or the D2 dopamine antagonists sulpiride (30 mg/kg, SC) or eticlopride (0.03 mg/kg, SC). Caffeine and d-amphetamine dose dependently increased locomotor activity. This effect of both caffeine and d-amphetamine was blocked by SCH23390 as well as by eticlopride. Sulpiride blocked the stimulatory effects of caffeine but not d-amphetamine. These results suggest that the locomotor stimulant effect of caffeine, like that of d-amphetamine, is mediated through dopaminergic systems; both D1 and D2 receptors appear to be involved.