Dopamine D1 rather than D2 receptor agonists disrupt prepulse inhibition of startle in mice

Abstract

Although substantialliterature describes the modulation of prepulse Inhibition (PPI) by dopamine (DA) in rats, few reports address the effects of dopaminergic manipulations on PPI in mice. We characterized the effects of subtype-specific DA agonists in the PPI paradigm tofurther delineate the specific influences of each DA receptor subtype on sensorimotor gating in mice. The mixed D1/D2 agonistapomorphine and the preferentialD1-family agonists SKF82958 and dihydrexidine significantly disrupted PPI, with differing or no effectson startle. In contrast to findings in rats, the D2/D3 agonist quinpirole reduced startle but had no effect on PPI. Pergolide, which hasaffinity for D2/D3 and D1-like receptors, reduced both startle and PPI, but only at the higher, nonspecific doses. In addition, the D1-familyreceptor antagonist SCH23390 blocked the PPI-disruptive effects of apomorphine on PPI, but the D2-family receptor antagonistraclopride failed to alter the disruptive effect of apomorphine. These studies revealpotentialspecies differences in the DA receptormodulation of PPI between rats and mice, where D1-family receptors may play a more prominent and independent role in themodulation of PPI in mice than in rats. Nevertheless, due to the limited selectivity of DA receptor agonists, further studies using specificreceptor knockout mice are warranted to clarify the respective roles of specific DA receptor subtypes in modulating PPI in mice. © 2003 American College of Neuropsychopharmacology.