Ambiguous-Cue Interpretation is Biased Under Stress- and Depression-Like States in Rats

Abstract

Negative cognitive biasFthe tendency to interpret ambiguous situations pessimisticallyFis a central feature of stress-related disorders such as depression. The underlying neurobiology of this bias, however, remains unclear, not least because of a lack of translational tools. We established a new ambiguous-cue interpretation paradigm and, with respect to the etiology of depression, evaluated if environmental and genetic factors contribute to a negative bias. Rats were trained to press a lever to receive a food reward contingent to one tone and to press another lever in response to a different tone to avoid punishment by electric foot-shock. In the ambiguous-cue test, the leverpress responses to tones with frequencies intermediate to the trained tones were taken as indicators for the rats' expectation of a positive or negative event. A negative response bias because of decreased positive and increased negative responding was found in congenitally helpless rats, a genetic animal model of depression. Moreover, treatment with a combined noradrenergic-glucocorticoid challenge, mimicking stress-related changes in endogenous neuromodulation, biased rats away from positive responding. This response shift was accompanied by neuronal activation in dentate gyrus and amygdala. Thus, environmental and genetic risk factors for depression induce a response bias, which resembles the pessimistic bias of patients suffering from depression. The behavioral paradigm described constitutes a useful tool to study the neuronal basis of decision making under ambiguous conditions and may promote innovative pharmaco-and psychotherapy for depression.

Evaluation of a novel translational task for assessing emotional biases in different species

“…Animals in a putative negative affective state made fewer positive responses and were slower to respond to cues predicting reward, suggesting decreased anticipation of positive events, which may be comparable with findings in human participants with emotional disorders (Wright & Bower, 1992). Using a similar tone-based task, Enkel et al (2010) further developed Harding et al's original task and showed that congenital learned helpless rats and acute pharmacological stress induced biases in their responding towards avoidance of punishment, further supporting a relationship between affective state and response bias in this task.…”

“…In relation to affective disorders, these issues represent a major hurdle to understanding disease pathologies and to the development of novel drug treatments (Frazer & Morilak, 2005;McArthur & Borsini, 2006). Recent studies have suggested that it is feasible to quantify emotion-related behaviours in animals (Enkel et al, 2010;Harding, Paul, & Mendl, 2004;Paul, Harding, & Mendl, 2005;Torres et al, 2005). Cognitive processes such as attention, memory, and judgment have been shown to be biased by underlying affective state (Leppänen, 2006).…”

Genetic Strain Differences in Learned Fear Inhibition Associated with Variation in Neuroendocrine, Autonomic, and Amygdala Dendritic Phenotypes

“…Precisely how this HPA-axis dysregulation might be a diathesis variable contributing to excessive fear in S1 remains a key question for future studies. For example, given recent evidence that elevating glucocorticoids promotes negative bias in rats (Enkel et al, 2010), it will be interesting to determine whether glucocorticoid abnormalities contribute to the fear generalization phenotype in S1.…”

A test to identify judgement bias in mice

“…Recently, the phenomenon of judgement bias has been investigated in several animal species, some being aimed at welfare assessment while others are more interested in judgement bias in animal models of human affective disorders [12][13][14][15][16][17][18][19][20][21][22][23].…”

“…For example, a tone of 2 kHz predicts a food reward and a tone of 4 kHz predicts an aversive white noise, in a test session the reaction of the animals to tones of 2, 3.5 and 4 kHz is investigated [13,21] by comparing this with the reaction to the positive and negative associated cues.…”