Evidence for specific interactions between 5-HT1A and dopamine D2 receptor mechanisms in the mediation of extrapyramidal motor functions in the rat.

Administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg kg-1 SC) completely antagonised the catalepsy produced by the dopamine (DA) D2 receptor antagonist raclopride (16 mg kg-1 SC). This effect by 8-OH-DPAT was in turn completely antagonised by treatment with the new 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin [(S)-UH-301] (3.5 mg kg-1 SC), but not by the mixed 5-HT1 receptor/beta-adrenoceptor antagonist (-)pindolol (2.0 mg kg-1 SC). The failure by (-)pindolol to antagonise the effects of 8-OH-DPAT on raclopride-induced catalepsy could be due to its beta-receptor-blocking properties, since by themselves both (-)pindolol and the selective beta-adrenoceptor antagonist betaxolol (4 mg kg-1 SC) at least partially antagonised the raclopride-induced catalepsy. The present results provide further support for specific interactions between 5-HT1A and DA D2 receptor mechanisms in the mediation of extrapyramidal motor functions in the rat.