Abstract
We compared anxiety, neuromotor, and cognitive functions in mutant rats with different allelic variants of dopamine transporter DAT knockout receiving balanced or excess in fat and fructose diet. The experiments were performed in DAT−/− homozygotes, DAT+/− heterozygotes, and DAT+/+ wild type rats. The genotype of DAT‐KO rats was confirmed by restriction analysis of DAT gene compared to behavioral responses in the open field test (OF). Animals in the first groups of each strain were fed a balanced AIN93M diet; and those in the second groups with a high‐fat/high‐fructose diet. Neuromotor function was studied as grip strength, and behavioral responses were assessed in the elevated plus maze and conditioned passive avoidance response tests. The mass of the internal organs and white and brown fat, as well as selected lipid and nitrogen metabolism parameters in blood plasma were determined at the end of the experiment. DAT−/− had the highest specific grip strength, and showed an increase in initial exploratory activity in comparison with DAT+/− and DAT +/+. The exploratory activity was significantly reduced in the second test compared to the first one in DAT−/− and DAT+/− of first but not second group. Anxiety decreased with age in the second groups of DAT+/− and DAT+/+ (but not in DAT−/−) and was higher in DAT+/+ than in DAT+/− and DAT−/−. Excess fat and fructose resulted in the deterioration of short‐term memory in DAT+/+. Lipidomic indices of blood plasma were less responsive to diet in DAT−/− and DAT−/+ in comparison to DAT+/+. The increased AsAT/AlAT activity ratio in DAT−/− compared with those in DAT+/+ suggests the activation of catabolism activity in the mutants. The consumption of excess fat and fructose significantly modified the effects produced by DAT gene allelic variants presumably due to the influence on the processes of dopamine metabolism.
Highlights
Dopamine and the dopaminergic system of the forebrain play a decisive role in the formation of satiety and food reward underlying food intake and eating behaviors (Auriemma et al 2018; Manning et al 2018; Ramos-Lopez et al 2018)
Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society
It can be seen that the dopamine transporter (DAT) À/À rats were characterized by markedly increased mobility, which was manifested in a unidirectional rapid movement within zone 4 of the arena
Summary
Dopamine and the dopaminergic system of the forebrain play a decisive role in the formation of satiety and food reward underlying food intake and eating behaviors (Auriemma et al 2018; Manning et al 2018; Ramos-Lopez et al 2018). According to a number of studies, the consumption of high-fat and high-carbohydrate diets, predisposing to obesity, causes persistent changes in the metabolism of dopamine, leading to disruption of the formation of a sense of food saturation (Lee et al 2010; Meyers et al 2017; Robertson and Rasmussen 2017) In this regard, dopaminergic mechanisms of food-related behavior are considered as promising targets for pharmacological interventions in the treatment of obesity, complementary to traditional dietary therapy, and lifestyle a 2019 The Authors. The use of animal lines with alterations in genes critical for the exchange of dopamine is a convenient way of assessing the roles of the dopaminergic system reflected in behavioral responses to food imbalances One such line is the DAT-KO rat strain, representing a knockout of the gene encoding the plasma membrane transporter of dopamine, DAT, which is responsible for its clearance from synapses of neurons (Efimova et al 2016; Cinque et al 2018). DAT-KO animals (both those homozygous and heterozygous for the defective gene) are an attractive model for studying the effects of a hypercaloric diet on food behavior mediated by dopaminergic neurons
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