Positive interaction between alpha-1 adrenergic and dopamine-2 receptors in locomotor activity of normo and supersensitive mice.

ABSTRACT

In normosensitive mice either the D1 antagonist SCH 23390 or the D2 antagonist sulpiride inhibited the reversion of reserpine-induced akinesia elicited by the mixed D1/D2 agonist pergolide. In mice rendered supersensitive by a five days' reserpine treatment, sulpiride did not prevent the pergolide-induced reversal of akinesia while SCH 23390 disclosed two subpopulations of mice. One population responded to pergolide with marked locomotor activity whereas in the other subpopulation this response was absent. However, all mice challenged with pergolide failed to reverse reserpine-akinesia after alpha-methyl-p-tyrosine (AMPT) pretreatment. The alpha 1/alpha 2 agonist clonidine restored the ability of pergolide to overcome reserpine akinesia in supersensitive mice pretreated with SCH 23390. Clonidine reversed the akinesia in supersensitive mice but in normal animals it did not. However, in these last conditions, the combined use of clonidine plus the D2 agonist LY 171555 was effective to induce locomotion. Neither AMPT nor SCH 23390 inhibited this response whereas the alpha-adrenergic antagonists prazosin and yohimbine did prevent it. The alpha 2 agonist B-HT 920 failed to induce locomotor responses when given together with LY 171555. The same occurred with the D1 agonist SKF 38393 when given together with clonidine. The combined use of SCH 23390 plus prazosin in chronic reserpinized mice prevented pergolide-induced locomotion. Adrenergic stimulation, acting on alpha 1 receptors, could be an alternative to D1 stimulation as a necessary factor to obtain D2-induced motor responses under normo and supersensitive conditions.