Sex-dependent alterations in behavior, drug responses and dopamine transporter expression in heterozygous DAT-Cre mice

  • Heterozygous mice that express Cre-recombinase under the dopamine transporter promoter (DAT-Cre knock in mice, or KI) are widely used for targeting midbrain dopamine neurons, under the assumption that their constitutive physiology is not affected. We report here that these mice display striking sex-dependent behavioral and molecular differences in relation to wildtypes (WT). Male and female KI mice were constitutively hyperactive, and male KI mice showed attenuated hyperlocomotor responses to amphetamine. In contrast, female KIs displayed a marked reduction in locomotion (“calming” effect) in response to the same dose of amphetamine. Furthermore, male and female DAT-Cre KI mice showed opposing differences in reinforcement learning, with females showing faster conditioning and males showing slower extinction. Other behavioral variables, including working memory and novelty preference, were not changed compared to WT. These effects were paralleled by differences in striatal DAT expression that disproportionately affected female KI mice. Our findings reveal clear limitations of the DAT-Cre line that must be considered when using this model.

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Author:Kauê Machado CostaORCiDGND, Daniela Schenkel, Jochen RoeperORCiD
Parent Title (English):Scientific reports
Publisher:Macmillan Publishers Limited, part of Springer Nature
Place of publication:[London]
Document Type:Article
Date of Publication (online):2021/02/08
Date of first Publication:2021/02/08
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/10/25
Tag:Basal ganglia; Genetic techniques; Learning and memory; Reward
Issue:art. 3334
Page Number:11
First Page:1
Last Page:11
This research was funded by the DFG CRC 1080 (A11). KMC received a fellowship and financial support from the Max Planck Society (International Max Planck Research School for Neural Circuits). Open Access funding enabled and organized by Projekt DEAL.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0