Alterations in the social-conditioned place preference and density of dopaminergic neurons in the ventral tegmental area in Clsnt2-KO mice
https://doi.org/10.18699/VJGB-23-14
Abstract
The incidence of autistic spectrum disorders (ASD) constantly increases in the world. Studying the mechanisms underlying ASD as well as searching for new therapeutic targets are crucial tasks. Many researchers agree that autism is a neurodevelopmental disorder. Clstn2-KO mouse strain with a knockout of calsyntenin 2 gene (Clstn2) is model for investigating ASD. This study aims to evaluate the social-conditioned place preference as well as density of dopaminergic (DA) neurons in the ventral tegmental area (VTA), which belongs to the brain reward system, in the males of the Clstn2-KO strain using wild type C57BL/6J males as controls. Social-conditioned place preference test evaluates a reward-dependent component of social behavior. The results of this test revealed differences between the Clstn2-KO and the control males, as the former did not value socializing with the familiar partner, spending equal time in the isolationand socializing-associated compartments. The Clstn2-KO group entered both compartments more frequently, but spent less time in the socializingassociated compartment compared to the controls. By contrast, the control males of the C57BL/6J strain spent more time in socializing-associated compartment and less time in the compartment that was associated with loneness. At the same time, an increased number of DA and possibly GABA neurons labeled with antibodies against the type 2 dopamine receptor as well as against tyrosine hydroxylase were detected in the VTA of the Clstn2-KO mice. Thus, a change in social-conditioned place preference in Clstn2-KO mice as well as a higher number of neurons expressing type 2 dopamine receptors and tyrosine hydroxylase in the VTA, the key structure of the mesolimbic dopaminergic pathway, were observed.
Supporting agencies: The work was partially funded by the budget project No. FWNR-2022-0023 of the Institute of Cytology and Genetics SB RAS (Novosibirsk, Russia) and the Russian Foundation for Basic Research (No. 20-015-00162). The studies were performed using the equipment of the Center for Genetic Resources of Laboratory Animals of the Federal Research Center of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, supported by the Ministry of Science and Higher Education of the Russian Federation (Unique identifier of the project RFMEFI62119X0023) and the Center for Microscopic Analysis of Biological Objects of the Siberian Branch of the Russian Academy of Sciences. The authors are grateful to T.N. Igonina for helpful discussions on the results and for the assistance in preparing the text of the manuscript
About the Authors
I. N. Rozhkova
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
S. V. Okotrub
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
E. Yu. Brusentsev
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
K. E. Uldanova
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
E. A. Chuyko
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
V. A. Naprimerov
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State Agricultural University
Russian Federation
Russian Federation
Novosibirsk
T. V. Lipina
University of Toronto
Canada
Canada
Toronto
T. G. Amstislavskaya
Scientific Research Institute of Neurosciences and Medicine
Russian Federation
Russian Federation
Novosibirsk
S. Ya. Amstislavsky
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
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