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Psychiatry Clin Neurosci. 2019 Jul 14. doi: 10.1111/pcn.12915. [Epub ahead of print]

The translational approach to apathy-like behavior in mice: from the practical point of view.

Author information

1
Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
2
Center for Kampo Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Abstract

Apathy is a pervasive clinical phenomenon that deserves more attention at the translational and pre-clinical levels. To study apathy-like behavior in mice, we relied on an operational definition of apathy: the quantitative reduction of voluntary, goal-directed behaviors. We recently found that the chronic loss-of-function of a specific cell type (striatal dopamine receptor type 2-expressing medium spiny neurons, D2-MSNs) within a restricted region (the ventrolateral striatum, VLS) was sufficient to induce apathy-like behavior in a food-seeking operant task. We further demonstrated that VLS D2-MSNs are activated at the preparatory period and optogenetic inhibition of VLS D2-MSNs during that period resulted in transient decreases in instrumental motivation, strengthening the hypothesis that VLS D2-MSNs mediate apathy-like behavior in mice. Mice bearing VLS D2-MSN dysfunction can thus be regarded as an apathy model for future translational studies. This article is protected by copyright. All rights reserved.

KEYWORDS:

fiberphotometry; goal-directed behavior; motivation; operant conditioning; optogenetics

PMID:
31304614
DOI:
10.1111/pcn.12915

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