Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats

Abstract

The stress response is essential to the survival of all species as it maintains internal equilibrium and allows organisms to respond to threats in the environment. Most stress research has focused on the detrimental impacts of stress on cognition and behavior. Reversal learning, which requires a change in response strategy based on one dimension of the stimuli, is one type of behavioral flexibility that is facilitated following some brief stress procedures. The current study investigated a potential mechanism underlying this facilitation by blocking glucocorticoid receptors (GRs) during stress. Thirty-seven male Long Evans rats learned to discriminate between two images on a touchscreen, one of which was rewarded. Once a criterion was reached, rats received stress (30 min of restraint stress or no stress) and drug (GR antagonist RU38486 or vehicle) administration prior to each of the first 3 days of reversal learning. We expected that stress would facilitate reversal learning and RU38486 (10 mg/kg) would prevent this facilitation in both early (<50% correct in one session) and late (>50% correct in one session) stages of reversal learning. Results showed that stressed rats performed better than unstressed rats (fewer days for late reversal, fewer correction trials, and fewer errors) in the late but not early stage of reversal learning. RU38486 did not block the facilitation of RL by stress, although it dramatically increased response, but not reward, latencies. These results confirm the facilitation of late reversal by stress in a touchscreenbased operant task in rats and further our understanding of how stress affects higher level cognitive functioning and behavior.

Constitutive differences in glucocorticoid responsiveness are related to divergent spatial information processing abilities

“…Therefore, it is plausible that superior performance in the High CORT line may involve AMPAR-dependent mechanisms and/or several of the other mechanisms mentioned above. Conversely, in agreement with the findings that stress affects reversal learning (Graybeal et al, 2011) and that glucocorticoids modulate mechanisms involved in reversal (Bryce and Howland, 2015; Myers et al, 2014; Raio et al, 2017), our data suggest that the Low CORT responding line may exhibit altered neural activity in key brain regions involved in flexible behaviors. In fact, our former analyses of these rats indicate that the Low line exhibits lower basal activity in the ventral orbitofrontal cortex (OFC), prefrontal cortex (mPFC) and hippocampus as compared to the High line (Walker and Sandi, 2018).…”

The neural basis of reversal learning: An updated perspective

“…A majority of studies in rodents report that reversal learning is insensitive to mPFC damage (Birrell and Brown, 2000, Bissonette et al, 2008, Floresco et al, 2008, Churchwell et al, 2009, Cordova et al, 2014) and can even be enhanced by lesions or stress-associated dysfunction in this region (Salazar et al, 2004, Graybeal et al, 2011, Bryce and Howland, 2015). Interestingly, several studies have suggested the mPFC may be recruited in reversal when attentional processes are taxed with difficult discriminanda (Bussey et al, 1997, Brigman and Rothblat, 2008), when multiple contingency changes are tracked continuously (Kosaki and Watanabe, 2012) or when discrete cues are coupled with a high visual or visuospatial component (Meunier et al, 1991, Li and Shao, 1998, Ragozzino et al, 1999, Chudasama and Robbins, 2003, Schwabe et al, 2004, Pickens et al, 2005, Young and Shapiro, 2009, Shaw et al, 2013).…”

Assessment of mGluR5 KO mice under conditions of low stress using a rodent touchscreen apparatus reveals impaired behavioural flexibility driven by perseverative responses

“…The reversal phase continued until mice reached more than 80% correct responses for 2 consecutive sessions. The early phase of reversal learning was analyzed through a summation of all the errors in each session (30 -correct trials) before each individual mouse reached 50% accuracy [7,10,24,25].…”

“…Exposure to aversive stimuli such as foot shock and forced swim can induce stress responses that affect learning, planning [6][7][8][9][10] and reward responsiveness [11,12], making it difficult for paradigms that use aversive stimuli to discriminate between stress susceptibility and cognitive rigidity. This is particularly important in studies of mGluR5, because mGluR5 is critical in resilience and the responses of mice to stressful stimuli [13,14].…”