Interaction between the effects of corticotropin-releasing factor and prepulse parameters on prepulse inhibition in two inbred rat strains and the F1 generation of a cross between them

Abstract

Levels of prepulse inhibition (PPI) depend on the interval between the startling and prepulse stimuli. Brown Norway rats show less PPI of the acoustic startle response than Wistar-Kyoto (WKY) rats when the interval between the prepulse and startling stimulus is 100 msec. Central administration of corticotropin-releasing factor (CRF) decreases PPI at this inter-stimulus interval. Here, the effect of CRF on PPI over a range of inter-stimulus intervals was examined in WKY and BN rats, and in the F1 generation of a cross between them. Rats received an intracerebroventricular infusion of either saline or CRF 30 min prior to testing PPI. Test trials included startle stimulus alone trials, and trials on which a prepulse stimulus of either 6, 12, or 15 dB above background preceded the startling stimulus by either 20, 75, 100, 500 or 2000 msec. CRF decreased PPI in WKY rats at all inter-stimulus intervals and all prepulse intensities, while the effect of CRF on PPI in BN rats only occurred at intermediate intervals. BN and WKY rats showed different levels of PPI only at the intermediate intervals. Baseline PPI in the F1 rats resembled the WKY phenotype. The CRF-induced change in PPI in the F1 generation has some qualities of the effects in each of the progenitor strains. These results suggest that both the effect of rats strain and of CRF on PPI depend on the inter-stimulus interval, and that there is an interaction between prepulse stimulus intensity and the inter-stimulus interval.

Restraint stress-induced reduction in prepulse inhibition in Brown Norway rats: Role of the CRF2 receptor

“…More studies are needed to determine whether the differences between the results of our studies and those of others are due to species effects (mice vs. rats), or are peculiar to the BN rats used here. Future studies will examine how pretreatment with selective CRF receptor antagonists affect the restraint-induced decrease in PPI in other rat strains such as the WKY rats, which are less sensitive to the effects of both exogenous CRF and stress than BN rats (Conti, 2005; Conti et al, 2002; Conti et al, 2009; Sutherland et al, 2010; Sutherland et al, 2008). These studies will reveal whether our findings generalize to other rat strains or whether our findings are unique to BN rats, which could perhaps make the BN rat a model for dysfunctional behavioral responses upon stress-induced activation of the CRF system.…”

“…This rat strain was chosen for several reasons. First, we have extensively characterized the effects of exogenously administered CRF on PPI and startle amplitude in BN rats (Conti, 2005; Conti et al, 2006; Conti et al, 2005; Conti et al, 2002; Conti et al, 2009; Sutherland et al, 2008). Thus, comparisons can be made between the findings of this study and our previously published studies.…”

Parametric approaches towards understanding the effects of the preferential D3 receptor agonist pramipexole on prepulse inhibition in rats

“…The recent emergence of drugs like PRA, which are preferential for D3 versus D2 receptors, has facilitated the study of D3 receptor systems in behavioral models. DA agonist effects on PPI are sensitive to many experimental variables, such as stimulus parameters (Mansbach et al, 1988; Weber and Swerdlow, 2008; Swerdlow et al, 2009), rat strain (Conti et al, 2009; Swerdlow et al, 2004; Weber et al, 2008; Weber and Swerdlow, 2008), sex (Lehmann et al, 1999; Swerdlow et al, 2008a) and estrous phase (Kinkead 2008; Koch, 1998), but most studies of the neurobiology of DA agonist effects on PPI proceeded without the benefit of knowing about these modifying experimental variables. The current studies were designed to “fill in the gaps” regarding parametric effects on PRA-induced PPI deficits in rats in advance of more detailed studies of the neurobiology of D3R effects on PPI.…”

“…Historically, studies of the neurobiology of these drug effects often have preceded studies that clarified the optimal experimental parameters; this sometimes led to interpretative difficulties (Conti et al, 2009; Davis, 1988; Davis et al, 1990; Kinney et al, 1999; Palmer et al, 2000; Swerdlow et al, 1998, 2008b). A more efficient strategy is to clarify the parametric sensitivity of drug effects in advance of embarking on complex neurobiological studies.…”

Cell type-specific modifications of corticotropin-releasing factor (CRF) and its type 1 receptor (CRF1) on startle behavior and sensorimotor gating

“…There were also seven 120 dB pulse alone trials. This block assesses the temporal processing window for prepulse effects on startle reactivity, since PPI is typically limited to a narrow temporal window (30–300 ms) that can be altered by CRF (Conti et al, 2009). The fifth block consisted of five 120 dB pulse trials.…”