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. 2014 Jan 16:8:1.
doi: 10.3389/fnhum.2014.00001. eCollection 2014.

Negative learning bias is associated with risk aversion in a genetic animal model of depression

Steven J Shabel  1 , Ryan T Murphy  1 , Roberto Malinow  1
Affiliations

Negative learning bias is associated with risk aversion in a genetic animal model of depression

Steven J Shabel et al. Front Hum Neurosci. .

Abstract

The lateral habenula (LHb) is activated by aversive stimuli and the omission of reward, inhibited by rewarding stimuli and is hyperactive in helpless rats-an animal model of depression. Here we test the hypothesis that congenital learned helpless (cLH) rats are more sensitive to decreases in reward size and/or less sensitive to increases in reward than wild-type (WT) control rats. Consistent with the hypothesis, we found that cLH rats were slower to switch preference between two responses after a small upshift in reward size on one of the responses but faster to switch their preference after a small downshift in reward size. cLH rats were also more risk-averse than WT rats-they chose a response delivering a constant amount of reward ("safe" response) more often than a response delivering a variable amount of reward ("risky" response) compared to WT rats. Interestingly, the level of bias toward negative events was associated with the rat's level of risk aversion when compared across individual rats. cLH rats also showed impaired appetitive Pavlovian conditioning but more accurate responding in a two-choice sensory discrimination task. These results are consistent with a negative learning bias and risk aversion in cLH rats, suggesting abnormal processing of rewarding and aversive events in the LHb of cLH rats.

Keywords: behavior; cLH; depression; helplessness; lateral habenula; reinforcement learning; reward; risk aversion.

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Figures

Figure 1
Figure 1
Negative learning bias in cLH rats. (A) cLH rats switched their preference away from the downshifted side more quickly than WT rats. (B) cLH rats switched their preference toward the upshifted side more slowly than WT rats. **P < 0.01; *P < 0.05. Student's t-tests on individual trial blocks. Error bars indicate s.e.m.
Figure 2
Figure 2
Risk-averse choice in cLH rats and its relationship to negative learning bias. (A) cLH rats chose the variable/risky side less than WT rats (averages of variable/risky better, even, and constant/safe better conditions used for comparison between groups). (B) cLH rats chose the variable/risky side less than WT rats in the variable/risky better condition, when risk was greatest. (C) Learning bias is correlated with risky choice. (D) Same as (C) with symbols denoting cLH (filled circles) and WT (open circles) groups. *P < 0.01. Student's t-test. Error bars indicate s.e.m.
Figure 3
Figure 3
Pavlovian conditioning and forced-choice accuracy. (A) Slower Pavlovian conditioning in cLH rats. (B) cLH rats responded more accurately during forced-choice trials with even, constant reward sizes on both sides. (C) Reaction time from lever press to sucrose delivery port during same forced-choice trials as in (B). *P < 0.01. Student's t-test on individual sessions in (A). Error bars indicate s.e.m.
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References

    1. Amat J., Sparks P. D., Matus-Amat P., Griggs J., Watkins L. R., Maier S. F. (2001). The role of the habenular complex in the elevation of dorsal raphe nucleus serotonin and the changes in the behavioral responses produced by uncontrollable stress. Brain Res. 917, 118–126 10.1016/S0006-8993(01)02934-1 - DOI - PubMed
    1. Caldecott-Hazard S. (1988). Interictal changes in behavior and cerebral metabolism in the rat: opioid involvement. Exp. Neurol. 99, 73–83 10.1016/0014-4886(88)90128-8 - DOI - PubMed
    1. Enkel T., Gholizadeh D., Von Bohlen Und Halbach O., Sanchis-Segura C., Hurlemann R., Spanagel R., et al. (2010a). Ambiguous-cue interpretation is biased under stress- and depression-like states in rats. Neuropsychopharmacology 35, 1008–1015 10.1038/npp.2009.204 - DOI - PMC - PubMed
    1. Enkel T., Spanagel R., Vollmayr B., Schneider M. (2010b). Stress triggers anhedonia in rats bred for learned helplessness. Behav. Brain Res. 209, 183–186 10.1016/j.bbr.2010.01.042 - DOI - PubMed
    1. Hasler G., Drevets W. C., Manji H. K., Charney D. S. (2004). Discovering endophenotypes for major depression. Neuropsychopharmacology 29, 1765–1781 10.1038/sj.npp.1300506 - DOI - PubMed

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