Avoidance perseveration during extinction training in Wistar-Kyoto rats: an interaction of innate vulnerability and stressor intensity

Abstract

Given that avoidance is a core feature of anxiety disorders, Wistar-Kyoto (WKY) rats may be a good model of anxiety vulnerability for their hypersensitivity to stress and trait behavioral inhibition. Here, we examined the influence of strain and shock intensity on avoidance acquisition and extinction. Accordingly, we trained WKY and Sprague-Dawley (SD) rats in lever-press avoidance using either 1.0-mA or 2.0-mA foot-shock. After extinction, neuronal activation was visualized by c-Fos for overall activity and parvalbumin immunoreactivity for gamma-aminobutyric acid (GABA) neuron in brain areas linked to anxiety (medial prefrontal cortex and amygdala). Consistent with earlier work, WKY rats acquired lever-press avoidance faster and to a greater extent than SD rats. However, the intensity of foot shock did not differentially affect acquisition. Although there were no differences during extinction in SD rats, avoidance responses of WKY rats trained with the higher foot shock perseverated during extinction compared to those WKY rats trained with lower foot shock intensity or SD rats. WKY rats trained with 2.0-mA shock exhibited less GABAergic activation in the basolateral amygdala after extinction. These findings suggest that inhibitory modulation in amygdala is important to ensure successful extinction learning. Deficits in avoidance extinction secondary to lower GABAergic activation in baslolateral amygdala may contribute to anxiety vulnerability in this animal model of inhibited temperament.

Figure 1

Avoidance lever-press of SD and WKY rats by sessions. Avoidance response in the phases of acquisition (12 sessions) and extinction (9 sessions) was expressed as avoidance ratio per session. Each session was composed of 20 trials. Avoidance lever-press increased during acquisition in both strains regardless of shock intensity, while WKY rats made more avoidance lever-presses than SD rats. However, during extinction, WKY rats extinguished slower as compared to SD rats in general. Higher shock intensity resulted in greater number of avoidance lever-press in WKY rats indicating resistance to extinguish. Each data point represents group mean ± S.E.M. (n=11–12/group).

Figure 2

Lever presses (ITRs) of SD and WKY rats during the first minute of safety period by session. Lever presses during the first minute of ITI (ITRs) was expressed as the number of responses in acquisition and extinction. WKY rats made more lever-presses compared to SD rats during early acquisition sessions. Higher shock intensity resulted in greater number of lever-presses during extinction in both strains. Each data point represents group mean ± S.E.M. (n=11–12/group).

Figure 3

Density of c-Fos (ir) cells in mPFC, namely anterior cingulate cortex (ACC), prelimbic (PL) and infralimbic (IL). Density of c-Fos (ir) cells in the mPFC, namely anterior cingulate cortex (ACC), prelimbic (PL) and infralimbic (IL), was depicted. WKY rats exhibited lower density of c-Fos (ir) cells in all three sub-regions as compared to SD rats (§, ps<0.05), regardless of intensity of foot shock. Data is expressed as group mean ± S.E.M. (n=5/group).

Figure 4

Double staining of c-Fos and PV in the basolateral amygdala (BA). Density of c-Fos (ir) and PV (ir) cells in the BA was depicted. C-Fos (ir) (arrow), PV (ir) (arrow head) and c-Fos/PV (ir) (block arrow) cells were visualized by DAB-NiCl₂, DAB and DAB/ DAB-NiCl₂ staining (100x) (a). C-Fos (ir) cell density did not differ between strains or conditions (b). However, WKY rats exhibited lower density of PV (ir) cells as compared to SD rats (§, p<0.05) (c). The proportion of double-labeled cells in PV (ir) cells was lower in rats trained under 2.0-mA shock (†, p<0.01); WKY rats trained under 2.0-mA shock exhibited lower ratio compared to their counterpart trained under 1.0-mA shock (*, post hoc p<0.05) (d). Data is expressed as group mean ± S.E.M. (n=5/group).