TY  - JOUR
A1  - Machado Costa, Kauê
A1  - Schenkel, Daniela
A1  - Roeper, Jochen
T1  - Sex-dependent alterations in behavior, drug responses and dopamine transporter expression in heterozygous DAT-Cre mice
T2  - Scientific reports
N2  - 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.
KW  - Basal ganglia
KW  - Genetic techniques
KW  - Learning and memory
KW  - Reward
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63682
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-636828
SN  - 2045-2322
N1  - 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.
VL  - 11
IS  - art. 3334
SP  - 1
EP  - 11
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -