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Article

Enhanced Dopamine Transmission and Hyperactivity in the Dopamine Transporter Heterozygous Mice Lacking the D3 Dopamine Receptor

1
Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia
2
St. Petersburg University Hospital, St. Petersburg State University, 199034 St. Petersburg, Russia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(21), 8216; https://doi.org/10.3390/ijms21218216
Received: 28 September 2020 / Revised: 23 October 2020 / Accepted: 27 October 2020 / Published: 3 November 2020
(This article belongs to the Special Issue Brain Neurotransmitters in Genetic Control of Behavior)
Dopamine transporter knockout (DATk) mice are known to demonstrate profound hyperactivity concurrent with elevated (5-fold) extracellular dopamine in the basal ganglia. At the same time, heterozygous DAT mice (DATh) demonstrate a 2-fold increase in dopamine levels yet only a marginal elevation in locomotor activity level. Another model of dopaminergic hyperactivity is the D3 dopamine receptor knockout (D3k) mice, which present only a modest hyperactivity phenotype, predominately manifested as stereotypical behaviors. In the D3k mice, the hyperactivity is also correlated with elevated extracellular dopamine levels (2-fold) in the basal ganglia. Cross-breeding was used to evaluate the functional consequences of the deletion of both genes. In the heterozygous DAT mice, inactivation of the D3R gene (DATh/D3k) resulted in significant hyperactivity and further elevation of striatal extracellular dopamine above levels observed in respective single mutant mice. The decreased weight of DATk mice was evident regardless of the D3 dopamine receptor genotype. In contrast, measures of thermoregulation revealed that the marked hypothermia of DATk mice (−2 °C) was reversed in double knockout mice. Thus, the extracellular dopamine levels elevated by prolonging uptake could be elevated even further by eliminating the D3 receptor. These data also suggest that the hypothermia observed in DATk mice may be mediated through D3 receptors. View Full-Text
Keywords: dopamine transporter; dopamine receptor; transgenic animals; hyperlocomotion; thermoregulation dopamine transporter; dopamine receptor; transgenic animals; hyperlocomotion; thermoregulation
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MDPI and ACS Style

Sotnikova, T.D.; Efimova, E.V.; Gainetdinov, R.R. Enhanced Dopamine Transmission and Hyperactivity in the Dopamine Transporter Heterozygous Mice Lacking the D3 Dopamine Receptor. Int. J. Mol. Sci. 2020, 21, 8216. https://doi.org/10.3390/ijms21218216

AMA Style

Sotnikova TD, Efimova EV, Gainetdinov RR. Enhanced Dopamine Transmission and Hyperactivity in the Dopamine Transporter Heterozygous Mice Lacking the D3 Dopamine Receptor. International Journal of Molecular Sciences. 2020; 21(21):8216. https://doi.org/10.3390/ijms21218216

Chicago/Turabian Style

Sotnikova, Tatyana D., Evgeniya V. Efimova, and Raul R. Gainetdinov 2020. "Enhanced Dopamine Transmission and Hyperactivity in the Dopamine Transporter Heterozygous Mice Lacking the D3 Dopamine Receptor" International Journal of Molecular Sciences 21, no. 21: 8216. https://doi.org/10.3390/ijms21218216

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