Alterations in cognitive flexibility in a rat model of post-traumatic stress disorder

George, Sophie; Rodriguez-Santiago, Mariana; Riley, John; Abelson, James L.; Floresco, Stan; Liberzon, Israel

doi:10.1016/j.bbr.2015.02.051

Cited by 50 publications

(39 citation statements)

References 70 publications

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“…Interestingly, impaired target detection in AB has been related to anxiety, but not depression, positive affect, or negative affect (e.g., Alderman et al, 2015; Van Dam, Earleywine, & Altarriba, 2012). This observed impairment in attention is consistent with a growing animal literature that suggests the deleterious effects from trauma exposure alone on cognitive functioning (e.g., George, Rodriguez-Santiago, Riley, Abelson, Floresco, & Liberzon, 2015). The localization of this impairment to trauma exposure rather than PTSD per se has also been found on attentional neuropsychological measures and sustained attentional tasks (e.g., Koenen, Driver, Oscar-Berman, Wolfe, Folsom, Huang, et al 2001; Stein, Kennedy, & Twamley, 2002).…”

Section: 5 Discussionsupporting

confidence: 90%

An analysis of inhibitory functioning in individuals with chronic posttraumatic stress disorder

Echiverri-Cohen

Zoellner

et al. 2016

Journal of Anxiety Disorders

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Cognitive abnormalities in posttraumatic stress disorder (PTSD) may be a function of underlying inhibitory deficits. Prepulse inhibition (PPI) and attentional blink (AB) are paradigms thought to assess inhibition. Using a sample of 28 individuals with PTSD compared to 20 trauma-exposed and 19 healthy individuals, PPI was examined using white noise that was preceded by a tone, and AB was examined using a presentation of letters in a stream of numbers. Relative to the control group, the PTSD and trauma-exposed groups did not follow the u-shaped pattern in AB, suggesting trauma-exposure and subsequent PTSD are associated with similar impairment in attention. Individuals with PTSD showed reduced PPI compared to trauma-exposed and healthy individuals, suggesting individuals with PTSD exhibit faulty automatic processing. For individuals with PTSD, PTSD severity was associated with a decline in PPI. These findings suggest a general faulty inhibitory mechanism associated with trauma exposure and PTSD.

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Section: 5 Discussionsupporting

confidence: 90%

An analysis of inhibitory functioning in individuals with chronic posttraumatic stress disorder

Echiverri-Cohen

Zoellner

et al. 2016

Journal of Anxiety Disorders

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“…Current conventional methods to assess estrous cycle in intact females require obtaining vaginal smears, which would have introduced stress as a variable. Since there is evidence that even brief stressors affect learning flexibility (Izquierdo et al 2006; George et al 2015), we did not introduce this assessment in the present experiment. Future, adequately-powered experiments should systematically examine the relationship of hormonal influences on these measures.…”

Section: Discussionmentioning

confidence: 99%

Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

Izquierdo

Pozos

Torre

et al. 2016

Behavioural Brain Research

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Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner.

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“…Based on this prior clinical work, the goal of the current studies was to test the utility of baclofen to specifically enhance behavioral flexibility. Indeed, impaired flexibility accompanies many neuropsychiatric diseases and can contribute to maladaptive perseverative behaviors and an inability to readily accomplish the activities of daily living (D'Cruz et al 2013; Enomoto et al 2011; Floresco et al 2009; Gass et al 2014; George et al 2015; Gruber et al 2010; Placek et al 2013). The current experiments demonstrate that acute systemic baclofen administration facilitates behavioral flexibility in rats, and suggest that this drug may be of utility for clinical conditions in which behavioral flexibility is impaired.…”

Section: Discussionmentioning

confidence: 99%

Effects of acute administration of the GABA(B) receptor agonist baclofen on behavioral flexibility in rats

2016

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RATIONALE The ability to adjust response strategies when faced with changes in the environment is critical for normal adaptive behavior. Such behavioral flexibility is compromised by experimental disruption of cortical GABAergic signaling, as well as in conditions such as schizophrenia and normal aging that are characterized by cortical hyperexcitability. The current studies were designed to determine whether stimulation of GABAergic signaling using the GABA(B) receptor agonist baclofen can facilitate behavioral flexibility. METHODS Male Fischer 344 rats were trained in a set-shifting task in which they learned to discriminate between two response levers to obtain a food reward. Correct levers were signaled in accordance with two distinct response rules (Rule 1: correct lever signaled by a cue light; Rule 2: correct lever signaled by its left/right position). The order of rule presentation varied, but they were always presented sequentially, with the trials and errors to reach criterion performance on the second (set shift) rule providing the measure of behavioral flexibility. Experiments determined the effects of the GABA(B) receptor agonist baclofen (i.p., 0, 1.0, 2.5 and 4.0 mg/kg) administered acutely before the shift to the second rule. RESULTS Baclofen enhanced set-shifting performance. Control experiments demonstrated that this enhancement was not simply due to improved discrimination learning, nor was it due to impaired recall of the initial discrimination rule. CONCLUSIONS The results demonstrate that baclofen can facilitate behavioral flexibility, suggesting that GABA(B) receptor agonists may have utility for treating behavioral dysfunction in neuropsychiatric disorders.

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Alterations in cognitive flexibility in a rat model of post-traumatic stress disorder

Cited by 50 publications

References 70 publications

An analysis of inhibitory functioning in individuals with chronic posttraumatic stress disorder

An analysis of inhibitory functioning in individuals with chronic posttraumatic stress disorder

Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

Effects of acute administration of the GABA(B) receptor agonist baclofen on behavioral flexibility in rats

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