A phosphoinositide-linked dopamine D1 receptor mediates repetitive jaw movements in rats

Abstract

Background: We have demonstrated that rats injected with D1 agonists SKF 38393 or A68930 demonstrate repetitive jaw movements (RJM). These agonist-induced movements in rats are similar in their appearance to those induced in rats by long-term treatment with antipsychotic drugs. Over recent years D-1 receptors were discovered which showed linkage not only to c-AMP but also to PI hydrolysis. We examined the effect of EEDQ inactivation of D1 receptors on D-1 mediated PI hydrolysis and RJM. Methods: Twenty four hours following EEDQ or vehicle administration D-1 agonists or vehicle were administered. The number of RJM episodes was assessed in EEDQ and vehicle treated rats. D-1 receptor density and inositol phosphate formation were determined in the striata. Results: EEDQ administration resulted, 24 hours later, in 70–80% selective depletion of D-1 receptors in the striata but did not modify the rate of RJM induced by D-1 agonists. There was no significant difference in D-1 mediated PI hydrolysis in EEDQ treated rats when compared to vehicle treated group. Conclusions: The present data support the earlier demonstration of D-1 agonist induced RJM, an effect mediated by a subpopulation of a D-1 receptor subtype and constitute the first behavioral evidence for the existence of a behavioral response mediated by D-1 like dopamine receptors linked to an alternate second messenger system-PI hydrolysis.