Comparison of Dopamine Receptor Antagonists on Hyperlocomotion Induced by Cocaine, Amphetamine, MK-801 and the Dopamine D1 Agonist C-APB in Mice

Rationale: Direct or indirect stimulation of dopamine receptors increases locomotor activity in mice. Determining the role played by D1 and D2 dopamine receptors in the mediation of this activity can be difficult due to the wide variety of experimental paradigms used to investigate these phenomena.

Objectives: This study set out to compare the role of selective antagonism of dopamine D1 and D2 receptors on the hyperactivity induced by a range of stimulants.

Methods: Mice were habituated to perspex locomotor activity boxes (30 x 30 x 30 cm) and activity was measured via photobeam interrupts.

Results: Haloperidol and clozapine both reduced the hyperactivity induced by MK-801. Haloperidol did so only at a dose that also decreased spontaneous activity (0.1 mg/kg), whereas clozapine reduced MK-801-induced hyperactivity at a dose that had no effect on spontaneous activity (1.25 mg/kg). The D1 antagonist SCH23390 (0.01 mg/kg) reduced hyperlocomotion induced by amphetamine (2.5 mg/kg), cocaine (10 mg/kg) and C-APB (1.0 mg/kg) at doses that did not consistently alter spontaneous activity, whereas the selective D2 antagonist raclopride only attenuated the hyperlocomotion induced by amphetamine, cocaine and C-APB at doses in excess of the minimum dose required to attenuate spontaneous locomotor activity significantly. The latency to peak levels of hyperlocomotion induced by MK-801 (0.3 mg/kg) was delayed by SCH23390 (0.1 mg/kg) but peak levels of activity were not reduced.

Conclusions: The results of the present study suggest that selective blockade of D1 receptors suppresses amphetamine and cocaine-induced hyperactivity in mice but not MK-801-induced locomotor activity.