engleski

Wistar-Zagreb 5HT rat : Possible animal model for autism

Autistic disorder is a behavioural sindrom characterized by impaired communication, impaired social interactions and repetitive interests and behaviours. Increased platelet serotonin level, as well as positive effect of serotonin reuptake inhibitors on some symptoms in autistic patients, have implicated the role of serotonergic neurotransmission in etiopathogenesis of autism. There are several animal models for autistic disorder, obtained by physical lesions of brain regions, by early intoxication/infection, or by gene knock-out. However, more specific model for this disorder would be overexpression of 5HT transporter, mimickingmore closely the situation in hyperserotonemic patients. By breeding selection for the extreme values of platelet 5HT level and platelet 5HT uptake, two sublines of Wistar-derived rats, with constitutionally high or low values of both parameters, have been developed (termed "high 5HT "subline and "low 5HT" subline, respectively). Molecular genetic studies demonstrated that the observed differences were underlain by differences in expression of platelet 5HT transporter between the sublines at both, protein and mRNA levels. Earlier behavioral tests indicated higher level of anxiety-related behavior in "high 5HT" subline in comparison to "low 5HT" subline. In this work we investigated social interaction as a measure of social anxiety. Tendency to explore novel animal was measured in open field as time spent in active contact within 10 minutes. Animals from "high- 5HT" subline showed significantly lower social interaction than the animals from "low-5HT" subline: 21636 vs. 27739 seconds spent in active contact (P<0.001, N&#188; ; 16 pairs per subline). The results demonstrate higher social anxiety in hyperserotonemic rat and implicate the use of Wistar-Zagreb 5HT rat as an original animal model of autistic disorder.

5HT transporter; rat; brain; behaviour; autism

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