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Inactivation of the prelimbic or infralimbic cortex impairs decision-making in the rat gambling task

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Abstract

Rationale

Studies employing the Iowa Gambling Task (IGT) demonstrated that areas of the frontal cortex, including the ventromedial prefrontal cortex, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex, and anterior cingulate cortex (ACC), are involved in the decision-making process. However, the precise role of these regions in maintaining optimal choice is not clear.

Objectives

We used the rat gambling task (rGT), a rodent analogue of the IGT, to determine whether inactivation of or altered dopamine signalling within discrete cortical sub-regions disrupts decision-making.

Methods

Following training on the rGT, animals were implanted with guide cannulae aimed at the prelimbic (PrL) or infralimbic (IL) cortices, the OFC, or the ACC. Prior to testing, rats received an infusion of saline or a combination of baclofen and muscimol (0.125 μg of each/side) to inactivate the region and an infusion of a dopamine D2 receptor antagonist (0, 0.1, 0.3, and 1.0 μg/side).

Results

Rats tended to increase their choice of a disadvantageous option and decrease their choice of the optimal option following inactivation of either the IL or PrL cortex. In contrast, OFC or ACC inactivation did not affect decision-making. Infusion of a dopamine D2 receptor antagonist into any sub-region did not alter choice preference.

Conclusions

Online activity of the IL or PrL cortex is important for maintaining an optimal decision-making strategy, but optimal performance on the rGT does not require frontal cortex dopamine D2 receptor activation. Additionally, these results demonstrate that the roles of different cortical regions in cost-benefit decision-making may be dissociated using the rGT.

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Acknowledgments

This work was supported by an operating grant awarded to CAW from the Canadian Institutes for Health Research (CIHR) and by National Institute on Drug Abuse Grant R01 DA022628 (LJMJV). CAW also receives salary support through the Michael Smith Foundation for Health Research and the CIHR New Investigator Award program. FDZ currently receives salary support through the CIHR Postdoctoral Fellowship. We thank Suzanne Lemstra and Ruth Damsteegt for practical assistance. CAW has previously consulted for Shire, and FDZ has previously consulted for Intervivo Solutions, Inc, both on unrelated matters. The authors declare no competing financial interests.

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Correspondence to Fiona D. Zeeb or Catharine A. Winstanley.

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Zeeb, F.D., Baarendse, P.J.J., Vanderschuren, L.J.M.J. et al. Inactivation of the prelimbic or infralimbic cortex impairs decision-making in the rat gambling task. Psychopharmacology 232, 4481–4491 (2015). https://doi.org/10.1007/s00213-015-4075-y

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