Role of Orbitofrontal Cortex and Differential Effects of Acute and Chronic Stress on Motor Impulsivity Measured With 1-Choice Serial Reaction Time Test in Male Rats

Abstract

Background Deficits in motor impulsivity, i.e. the inability to inhibit a prepotent response, are frequently observed in psychiatric conditions. Several studies suggest that stress often correlates with higher impulsivity. Among the brain areas affected by stress, the orbitofrontal cortex (OFC) is notable because of its role in impulse control. OFC subregions with unique afferent and efferent circuitry play distinct roles in impulse control, yet it is not clear what OFC subregions are engaged during motor impulsivity tasks. Methods In this study we used a rodent test of motor impulsivity, the 1-choice serial reaction time test, to explore activation of OFC subregions during either a well-learned motor impulsivity task, or in a challenge task with a longer wait time that increases premature responding. We also examined the effects of acute inescapable stress (IS), chronic intermittent cold stress (CIC) and chronic unpredictable stress (CUS) on motor impulsivity. Results Fos expression increased in the lateral OFC and agranular insular cortex during performance in both the mastered and the challenge condition. In the ventral OFC, Fos expression increased only during challenge, and within the medial OFC, Fos was not induced in either condition. IS produced a transient effect on premature responses in the mastered task, whereas CIC stress and CUS altered premature responses in both conditions in ways that were specific to each stressor. Conclusions These results suggest that different OFC subregions have different roles in motor impulse control, and the effects of stress vary depending on the nature and duration of the stressor.

Activation of the mPFC-NAc pathway reduces motor impulsivity but does not affect risk-related decision-making in innately high-impulsive rats

“…This is the first study to investigate differences in brain metabolism using [ 18 F]FDG and PET imaging in high vs. low impulsive rats. We observed that RHA rats exhibited lower [ 18 F]FDG uptake in brain regions that have been associated with impulsive behaviors, such as the mPFC 26,44 , NAc 19 , OFC 45 and thalamus 46 . This is consistent with clinical data showing lower cortical glucose metabolism in patients with ADHD 47 or borderline personality disorders [48][49][50] , who also display low impulse control 51 .…”

Acute stress differentially alters reward-related decision making and inhibitory control under threat of punishment

“…Treatment with the α2 adrenergic antagonist and pharmacological stressor yohimbine impairs “waiting”, as indexed by increased premature responses on the 5-CSRTT ( Adams et al, 2017 ; Baek et al, 2017 ; Barlow et al, 2018 ; Broos et al, 2017 ; Chernoff et al, 2021 ; Sun et al, 2010 ) and higher response rates on a DRL task ( Sanger, 1988 ), both of which reduced opportunities to obtain rewards. Similarly, cold stress also increases DRL responding ( Thomas et al, 1991 ), and inescapable shock stress increases premature response on a 1-CSRTT ( Girotti et al, 2022 ). These previous findings, in combination with the present data suggest that in males, acute stress impairs response inhibition in a variety of circumstances, where premature responses may either delay reward delivery or result in more explicit punishments.…”