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

Abstract

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. 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. 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. 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. 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.