Abstract
As a model of anxiety disorder vulnerability, male Wistar-Kyoto (WKY) rats acquire lever-press avoidance behavior more readily than outbred Sprague-Dawley rats, and their acquisition is enhanced by the presence of a discrete signal presented during the inter-trial intervals (ITIs), suggesting that it is perceived as a safety signal. A series of experiments were conducted to determine if this is the case. Additional experiments investigated if the avoidance facilitation relies upon processing through medial prefrontal cortex (mPFC). The results suggest that the ITI-signal facilitates acquisition during the early stages of the avoidance acquisition process, when the rats are initially acquiring escape behavior and then transitioning to avoidance behavior. Post-avoidance introduction of the visual ITI-signal into other associative learning tasks failed to confirm that the visual stimulus had acquired the properties of a conditioned inhibitor. Shortening the signal from the entirety of the 3 min ITI to only the first 5 s of the 3 min ITI slowed acquisition during the first four sessions, suggesting the flashing light (FL) is not functioning as a feedback signal. The prelimbic (PL) cortex showed greater activation during the period of training when the transition from escape responding to avoidance responding occurs. Only combined PL + infralimbic cortex lesions modestly slowed avoidance acquisition, but PL-cortex lesions slowed avoidance response latencies. Thus, the FL ITI-signal is not likely perceived as a safety signal nor is it serving as a feedback signal. The functional role of the PL-cortex appears to be to increase the drive toward responding to the threat of the warning signal. Hence, avoidance susceptibility displayed by male WKY rats may be driven, in part, both by external stimuli (ITI signal) as well as by enhanced threat recognition to the warning signal via the PL cortex.
Highlights
Anxiety disorders are a product of experience and underlying vulnerabilities (Merikangas et al, 1999)
These failed to detect any difference in the amount of responding during the inter-trial intervals (ITIs) that was attributable to the presence/absence of the flashing light (FL) during the ITI
The paradoxical behavioral inhibition and active-avoidance susceptibility demonstrated by WKY rats provide a unique opportunity to examine how an intact, albeit abnormal, brain can produce behaviors akin those expressed by individuals with pathological anxiety
Summary
Anxiety disorders are a product of experience and underlying vulnerabilities (Merikangas et al, 1999). The underlying source of avoidance susceptibility is unknown, but it may involve inherent differences in the perception of threat versus safety. Individuals with anxiety disorders commonly do not react to signals associated with safety in the same manner as controls (Rachman, 1984; Grillon, 2002; Schmidt et al, 2006; Lohr et al, 2007; Jovanovic et al, 2010), and regions of prefrontal cortex that have been implicated in the perception of threat versus safety in animals may be involved in the expression of anxiety disorders (Schiller et al, 2008). A model system that can show both prefrontal cortex activation and threat-signal and/or safety-signal influences upon the acquisition of avoidance behavior would be advantageous in order to gain a greater understanding of potential sources of anxiety vulnerability
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