Analysis of behavioral structure in dopamine transporter knockout rats

BACKGROUND: Animals with knockout of the dopamine transporter gene (DAT-KO) reproduce the main symptoms of attention deficit disorder with hyperactivity in children. Alterations in DAT function in DAT-KO rats represent a key mechanism in various pathological conditions associated with hyperdopaminergia. The main behavioral phenomena have been studied only in homozygous DAT-KO gene knockout rats, but have not been studied in heterozygotes with a similar gene knockout. AIM: This work aimed to investigate the specificity of behavioral pattern expression in response to novelty in free behavior in DAT-KO rats compared with heterozygous animals for the knockout gene (DAT-HET) and wild-type (WT) rats. METHODS: Experiments were conducted on 57 male Wistar rats (DAT-KO, DAT-HET, and WT). Rats with DAT gene knockout were originally obtained from Saint Petersburg State University, Institute of Translational Biomedicine. Genotyping and behavioral assessment in the open field test were performed. Behavioral pattern analysis included locomotion; sniffing; rearing; grooming; movement in place (changes in head and body coordinates within a conditional circle centered on relatively immobile hind limbs); hole exploration; and wall-supported rearing (vertical stance with forelimb support against the wall of the open field). RESULTS: DAT-KO rats, compared with WT and DAT-HET rats, demonstrated pronounced hyperactivity, spent less time in the center of the field, and moved in a repetitive circular pattern along the walls. Exploratory activity in DAT-KO rats was reduced, as evidenced by fewer hole exploration and sniffing acts compared with WT and DAT-HET rats. Anxiety-related behavior in DAT-KO rats was reduced, as indicated by fewer grooming acts and movements in place. DAT-HET rats showed increased locomotor and exploratory activity compared with WT rats. CONCLUSION: Based on our findings and data from other studies, it is concluded that behavioral disinhibition represents an overlapping feature of addictive behavior components (impulsivity and compulsivity), which require independent investigation in DAT-KO animals. The presence of hyperdopaminergia, increased locomotor and exploratory activity in DAT-HET rats, together with impaired cognitive function, may predict the development of addictive behavioral disorders under conditions of gene–environment interaction.