The effects of dopamine D2 and D3 antagonists on spontaneous motor activity and morphine-induced hyperactivity in male mice

Abstract

Rationale: Dopaminergic neurotransmission, in particular the mesolimbic pathway, is involved in spontaneous locomotor activity and in morphine-induced hyperactivity, since the drugs acting on DA receptors can modify the action of morphine and this effect could be dependent on the type of DA receptor affected. Objective: In this study, the action of U-99194A maleate, haloperidol, sulpiride and morphine (5, 10, 20, 40 mg/kg) on locomotor activity in male mice was evaluated. Likewise, the effects of these dopaminergic antagonists on morphine-induced hyperactivity were studied. Methods: Animals treated with U-99194A maleate (2.5, 5, 10, 20 mg/kg), haloperidol (0.075, 0.1 mg/kg), sulpiride (20, 40 mg/kg), or morphine (5, 10, 20, 40 mg/kg), and animals treated with these neuroleptics plus morphine were tested in an actimetre at different time points. Results: It was found that an increase in locomotor activity was produced between 0 and 30 min after the administration of 20 mg/kg U-99194A maleate and between 30 and 60 min after the administration of 20 and 40 mg/kg morphine. This dose of U-99194A maleate and the high dose of sulpiride reverts the hyperactivity induced by 20 mg/kg morphine. Haloperidol reversed the hyperactivity induced by all doses of morphine. Conclusions: Our results confirm that the action of DA D₂ and D₃ receptors could be dependent on the dopaminergic state, in this case modified by the action of morphine.