Crawford, Dylan William. Unpredictable mixed-valence reinforcement promotes a generalized anxiety-like state in genetically heterogeneous mice. Retrieved from https://doi.org/doi:10.7282/t3-zx22-3e89
DescriptionAnxiety, an emotion that can be protective to an individual during adverse conditions, has the ability to reach levels of psychopathology in humans when left unchecked. This increasingly common psychopathological outcome has led to increasing attention from the fields of psychology and neuroscience in the continued search for clinically relevant treatment options. As a necessity to investigating novel clinical treatment options, psychologists have been tasked with developing animal laboratory models to approximate clinical anxiety. While there have been a plethora of attempts to model this psychopathology, we find that many previously described models fail to make sufficient contact with the etiology and descriptions of anxiety disorders in humans. Here we describe three studies aimed at developing a novel rodent model wherein mice exhibit anxiety-like behaviors through behavioral manipulations meant to approximate anxiety-inducing circumstances in humans. Animals were chronically subjected to conditioning manipulations in which behavioral responses or cues were paired with unpredictable reward or punishment aimed at inducing a chronic state of “apprehensive expectation”. Animals’ pre- and post-manipulation anxiety-like behaviors were assessed using batteries of behavioral measures including an open field, light/dark box, elevated plus maze, social boxes, startle response, marble burying, and corticosterone assay. In studies that used an operant conditioning manipulation wherein the animal made active choices to engage with the stimuli (Studies 1 and 3), we found that animals exhibited significantly more anxiety-like behaviors after the behavioral experience with mixed valance reinforcement. In contrast, a study using a similar procedure with a classical conditioning manipulation (wherein the animals were passively exposed to stimuli; Study 2) resulted in no significant change in anxiety-like behaviors from pre-manipulation levels. In total, the results provide support that a specific cognitive state induction (achieved specifically through active engagement with unpredictable mixed-valance stimuli) may be sufficient to induce a chronic generalized anxiety in mice.