Heritable strain differences in sensitivity to the startle gating-disruptive effects of D2 but not D3 receptor stimulation

Abstract

Prepulse inhibition (PPI) of the startle reflex is an operational measure of sensorimotor gating that is deficient in several brain disorders and is disrupted in rats by dopamine (DA) agonists. Robust heritable strain differences are observed between Sprague-Dawley (SD) and Long-Evans (LE) strains in sensitivity to the PPI-disruptive effects of DA agonists associated with differential gene expression in the nucleus accumbens. Here, we compared the contribution of D2 versus D3 receptors with this heritable difference, using the D3-preferential agonist (pramipexole), the mixed D3/D2 agonist (quinpirole), the mixed D1/D2-like agonist (apomorphine), and the preferential D2 antagonist (L741,626). All DA agonists disrupted PPI in SD and LE rats. Greater sensitivity for this effect was evident with apomorphine and quinpirole in SD than LE rats, but not with pramipexole. The selective D2 antagonist L741,626 preferentially reversed apomorphine-induced PPI deficits at a dose that did not alter pramipexole-induced PPI deficits. We conclude that the heritable pattern of greater PPI 'disruptability' by DA agonists in SD versus LE rats reflects differences in D2 but not D3 receptor-associated mechanisms.