Objective: The perseveration of avoidance behavior, even in the absence of once threatening stimuli, is a key feature of anxiety and related psychiatric conditions. This phenomenon can be observed in the Wistar-Kyoto (WKY) rat which, in comparison to outbred controls, demonstrates impaired extinction of avoidance behavior. Also characteristic of the WKY rat is abnormalities of the neurocircuitry and neuroplasticity of the medial prefrontal cortex (mPFC).
View Article and Find Full Text PDFIndividuals exhibiting an anxiety disorder are believed to possess an innate vulnerability that makes them susceptible to the disorder. Anxiety disorders are also associated with abnormalities in the interconnected brain regions of the amygdala and prefrontal cortex (PFC). However, the link between anxiety vulnerability and amygdala-PFC dysfunction is currently unclear.
View Article and Find Full Text PDFAltered medial prefrontal cortex (mPFC) and amygdala function is associated with anxiety-related disorders. While the mPFC-amygdala pathway has a clear role in fear conditioning, these structures are also involved in active avoidance. Given that avoidance perseveration represents a core symptom of anxiety disorders, the neural substrate of avoidance, especially its extinction, requires better understanding.
View Article and Find Full Text PDFInbred Wistar Kyoto (WKY) rats express inhibited temperament, increased sensitivity to stress, and exaggerated expressions of avoidance. A long-standing observation for lever press escape/avoidance learning in rats is the duration of the warning signal (WS) determines whether avoidance is expressed over escape. Outbred female Sprague-Dawley (SD) rats trained with a 10-s WS efficiently escaped, but failed to exhibit avoidance; avoidance was exhibited to a high degree with WSs longer than 20-s.
View Article and Find Full Text PDFAs 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).
View Article and Find Full Text PDFFront Behav Neurosci
October 2014
Avoidance is a core feature of anxiety disorders and factors which increase avoidance expression or its resistance represent a source of vulnerability for anxiety disorders. Outbred female Sprague Dawley (SD) rats and inbred male and female Wistar-Kyoto (WKY) rats expressing behaviorally inhibited (BI) temperament learn avoidance faster than male SD rats. The training protocol used in these studies had a longstanding interpretive flaw: a lever-press had two outcomes, termination of the warning signal (WS) and prevention of foot shock.
View Article and Find Full Text PDFAvoidance and its perseveration represent key features of anxiety disorders. Both pharmacological and behavioral approaches (i.e.
View Article and Find Full Text PDFFront Behav Neurosci
August 2014
The hippocampus has been implicated in anxiety disorders and post-traumatic stress disorder (PTSD); human studies suggest that a dysfunctional hippocampus may be a vulnerability factor for the development of PTSD. In the current study, we examined the effect of hippocampal damage in avoidance learning, as avoidance is a core symptom of all anxiety disorders. First, the effect of hippocampal damage on avoidance learning was investigated in outbred Sprague Dawley (SD) rats.
View Article and Find Full Text PDFAvoidance susceptibility may constitute a vulnerability to develop anxiety disorders, and Wistar-Kyoto (WKY) rats exhibit unique features in their acquisition of avoidance behavior that appear to promote susceptibility to this form of learning, namely the absence of the commonly observed "warm-up" effect. The present study sought to determine if strain differences in acquired avoidance behavior, between WKY and Sprague Dawley rats, could be attributed to differences in dopamine-related plasticity, represented by extracellular signal-regulated kinase (ERK) activity, and prolonged neuronal activation, represented by ΔFosB accumulation, in three key areas of the brain: the medial prefrontal cortex (mPFC), dorsal striatum (DS), and basolateral amygdala (BLA). Consistent with earlier work, WKY rats exhibited a higher level of asymptotic performance of avoidance behavior, which included an absence of warm-up in the first few trials of later training sessions, and they exhibited more non-reinforced anticipatory responses in the single minute prior to the initiation of the first warning signal presentation of each training session.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
August 2011
Rats that exhibit a behaviorally inhibited temperament acquire active-avoidance behaviors quicker, and extinguish them slower, than normal outbred rats. Here we explored the contribution of stimuli that signal periods of non-threat (i.e.
View Article and Find Full Text PDFGiven 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.
View Article and Find Full Text PDFThe medial septum and diagonal band (MSDB) are important in spatial learning and memory. On the basis of the excitotoxic damage of GABAergic MSDB neurons, we have recently suggested a role for these neurons in controlling proactive interference. Our study sought to test this hypothesis in different behavioral procedures using a new GABAergic immunotoxin.
View Article and Find Full Text PDFWistar-Kyoto (WKY) rats, an animal model of anxiety vulnerability, acquire lever-press avoidance faster than outbred Sprague-Dawley (SD) rats. Faster avoidance acquisition may reflect an inherent ability to acquire cue-outcome associations, response-outcome associations or both. To evaluate cue-outcome learning, acquisition of classically conditioned eyeblink response was compared in SD and WKY rats using a delay-type paradigm (500-ms conditioned stimulus (CS) coterminating with a 10-ms unconditional stimulus (US)).
View Article and Find Full Text PDFWistar-Kyoto (WKY) rats exhibit behavioral inhibition and model anxiety vulnerability. Although WKY rats exhibit faster active avoidance acquisition, simple associative learning or the influence of proactive interference (PI) has not been adequately assessed in this strain. Therefore, we assessed eyeblink conditioning and PI in WKY and outbred Sprague-Dawley (SD) rats.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
August 2010
The risk for developing anxiety disorders is greater in females and those individuals exhibiting a behaviorally inhibited temperament. Growth of behavioral avoidance in people is a significant predictor of symptom severity in anxiety disorders, including post-traumatic stress disorder. Using an animal model, our lab is examining how the process of learning avoidant behavior may lead certain individuals to develop anxiety.
View Article and Find Full Text PDFTailshock stress causes transient reductions in startle reactivity, associative learning and open field activity in female rats in an ovarian hormone dependent manner. Others have shown estrogen modulation of associative learning by testing across the estrus cycle and pharmacological manipulations. Here we tested whether stress-induced suppression of startle reactivity can be attributed to circulating ovarian hormones.
View Article and Find Full Text PDFCombinations of drugs approved to treat Alzheimer's disease (AD) were tested in older rabbits with delay eyeblink classical conditioning, a form of associative learning severely impaired in AD. In Experiment 1 (n=49 rabbits), low doses (0.1, 0.
View Article and Find Full Text PDFPyridostigmine bromide (PB), a peripheral cholinesterase inhibitor, has been shown to support odor-potentiated startle responding in rats. Here we conducted 2 sets of experiments that further characterize aspects of this learned association. First we conducted experiments designed to further characterize the learning parameters of the odor-PB association that leads to startle facilitation weeks later.
View Article and Find Full Text PDFThe dopamine (DA) pathway mediates numerous neuronal functions which are implicated in psychiatric disorders. Previously, our lab investigated the status of the dopamine transporter in the Wistar-Kyoto rat, a purported rodent model of depressive behavior, and reported significant alterations in transporter binding sites in several brain regions when compared to control rat strains. Given that DA-2 and DA-3 receptors belong to the same class of DA receptors, are co-localized in the mesolimbic and nigrostriatal regions of the brain and function as autoreceptors, this study mapped the distribution of central DA-2 and DA-3 receptors in Wistar-Kyoto and Wistar rats.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
January 2006
The Wistar Kyoto (WKY) rat has been proposed as an animal model of depressive behavior. Exposing WKY rats to stress stimulation produces symptoms such as anhedonia, psychomotor retardation, ambivalence and negative memory bias. Given the role of the mesolimbic dopamine (DA) system in cognitive, emotional and motivational behaviors, we previously examined the distribution of DA transporter (DAT) sites in the brains of WKY compared to Wistar (WIS) and Sprague-Dawley (S-D) rats.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
September 2003
The Wistar Kyoto (WKY) rat has long been proposed as an animal model of depressive behavior. Exposure to stress produces symptoms such as anhedonia, psychomotor retardation, ambivalence, and negative memory bias. Autoradiographic studies have revealed significant differences in the density of norepinephrine transporter (NET) and serotonin transporter (5-HTT) sites in several brain regions in WKY rats compared to Sprague-Dawley (S-D) rats.
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