In rats with a unilateral lesion of the nigrostriatal dopaminergic pathway, the ipsilateral rotation produced by the enhanced actions of endogenous dopamine (DA) on the nonlesioned side, induced by either the DA-releasing drug amphetamine or the DA uptake inhibitor GBR 13069, was blocked effectively by pretreatment with either the selective D1 DA receptor antagonist, SCH 23390, or the D2 selective antagonist, haloperidol. In contrast, contralateral rotation produced by apomorphine or l-dihydroxy-phenylalanine, which lead to the preferential activation of D1 and D2 receptors on the lesioned side, was effectively prevented only when both receptor subtypes were inhibited. The results of these experiments demonstrate that the interaction between D1 and D2 receptors in the lesioned side differs from that in the nonlesioned side. Whereas the simultaneous stimulation of both DA receptor subtypes in the normally innervated basal ganglia is required for the production of turning behavior, the stimulation of either subtype alone in the dopaminergic denervated side can produce rotation. However, the concurrent administration of the D1 agonist, SKF 38393, with the D2 agonist, LY 171555, produced a synergistic effect on contralateral rotation. These results suggest that there is preservation of at least some functional interaction between D1 and D2 receptors in the lesioned basal ganglia but that there may be in addition a mechanism by which the two receptor subtypes can function independently of each other. The unilaterally lesioned rat appears to be a very good model in which to study the interaction between D1 and D2 receptors under conditions of both normal innervation and of DA denervation. Furthermore, this model can be used effectively to test the interactions between new DA agonists and antagonists in both situations in the same animal.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1988|
All Science Journal Classification (ASJC) codes
- Molecular Medicine