Heritable differences in the effects of amphetamine but not DOI on startle gating in albino and hooded outbred rat strains

Strain differences in the disruption of prepulse inhibition of startle after systemic and intra-accumbens amphetamine administration

“…We also previously reported greater sensitivity to the PPI-disruptive effects of systemically administered AMPH in SD vs. LE rats (Swerdlow et al 2003a), and this effect was reproduced in the present Experiment 1. These strain differences were tested after intracerebral AMPH infusion in Experiment 2, and perhaps the simplest interpretation of the present data is that SD > LE differences in systemic AMPH sensitivity are reproduced within the NAC core, where infusion of AMPH caused a statistically significant disruption of PPI in SD rats (and in F1 rats) but not in LE rats.…”

“…We previously reported that PPI is disrupted in SD rats by AMPH, after systemic administration and after intra-NAC infusion (Wan et al 1995;Wan & Swerdlow 1996;Swerdlow et al 2003a); both of these effects were observed in the present study. A relative anatomical specificity for this effect of AMPH was evident in the present studies, with infusion into the NAC core (medial or lateral regions) causing a significant loss of PPI in SD rats, while infusion into other forebrain regions had only modest effects on PPI, that did not reach statistical significance.…”

“…As we have observed after intracerebral infusion of the DA antagonist haloperidol (Hart et al 1998), the pattern of dose effects on PPI after localized infusion of AMPH into any one of several DA terminal subregions does not fully reproduce that observed after systemic drug administration. For example, after localized intra-NACc AMPH infusion, SDxLE F1 rats exhibit a PPI phenotype comparable to SD rats ( Figure 4A), while systemic AMPH injection yields an F1 phenotype that is intermediate between parental strains (Swerdlow et al 2003a). We can speculate that dopaminergic changes within multiple subregions contribute to strain differences in reduced PPI after systemic drug administration, even though in isolation (after localized infusion), the contribution of any single region does not achieve statistical significance; this speculation would be consistent with our findings that differences in DA-stimulated GTPγS binding between SD and LE rats are observed not only within the NAC, but also within the AMS and cortical regions (Swerdlow et al 2006a), consistent with anatomically distributed genetically-based differences in dopaminergic function.…”

“…amphetamine: AMPH), compared to hooded Long Evans rats from Harlan Laboratories (LE) (Swerdlow et al 2003a(Swerdlow et al ,2004a. These differences are innate (Swerdlow et al 2004a,c) and neurochemically specific (Swerdlow et al 2003(Swerdlow et al ,2004b, follow relatively simple inheritance patterns (Swerdlow et al 2003a(Swerdlow et al ,2004c, cannot be explained by differences in maternal behavior (Swerdlow et al 2004a), and appear to be linked to the inheritance of coat pigmentation (Swerdlow et al 2004c and DA-linked G-protein function (Swerdlow et al 2006a).…”

Heritable Differences in the Dopaminergic Regulation of Behavior in Rats: Relationship to D2-Like Receptor G-Protein Function

“…Braff et al, 2001); in rats, PPI is disrupted by dopamine (DA) agonists, including the direct DA agonist, apomorphine (APO), and the indirect DA agonist, amphetamine (AMPH) (Swerdlow et al, 1986;Mansbach et al, 1988). Heritable differences in PPI sensitivity to DA agonists have been identified in outbred rat strains (Swerdlow et al, 2003(Swerdlow et al, , 2004a. For example, crosses and backcrosses between Harlan Sprague-Dawley (SD) and Harlan Long Evans (LE) rats revealed an orderly pattern of PPI APO sensitivity (SD4N24F14LE), suggestive of the additive effects of a relatively small number of genes (Swerdlow et al, 2004a, b).…”