Motor transitions’ peculiarity of heterozygous DAT rats when offspring of an unconventional KOxWT mating

Carla Cannizzaro, Anna Brancato, Sara Lucia Maria Lo Russo, Adinolfi Annalisa, Carbone Cristiana, Alleva Enrico, Adriani Walter

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1 Citation (Scopus)

Abstract

Causal factors of psychiatric diseases are unclear, due to gene×environmentinteractions. Evaluation of consequences, after a dopamine-transporter (DAT) gene knock-out (DATKO),has enhanced understanding the pathological dynamics of several brain disorders, such asAttention-Deficit/Hyperactivity and Bipolar-Affective disorders. Recently, our attention has shiftedto DAT hypo-functional (heterozygous, HET) rodents: HET dams display less maternal care and HETfemales display marked hypo-locomotion if cared by HET dams (Mariano et al., 2019). We assessedphenotypes of male DAT-heterozygous rats as a function of their parents: we compared “maternal”origin (MAT-HET, obtained by breeding KO-male rats with WT-female dams) to “mixed” origin(MIX-HET, obtained by classical breeding, both heterozygous parents) of the allele. MAT-HETsubjects had significantly longer rhythms of daily locomotor activity than MIX-HET and WT-controlsubjects. Furthermore, acute methylphenidate (MPH: 0, 1, 2 mg/kg) revealed elevated threshold forlocomotor stimulation in MAT-HETs, with no response to the lower dose. Finally, by Porsolt-Test,MAT-HETs showed enhanced escape-seeking (diving) with more transitions towards behavioraldespair (floating). When comparing both MAT- and MIX-HET to WT-control rats, decreased levelsof DAT and HDAC4 were evident in the ventral-striatum; moreover, with respect to MIX-HETsubjects, MAT-HET ones displayed increased DAT density in dorsal-striatum. MAT-HET ratsdisplayed region-specific changes in DAT expression, compared to “classical” MIX-HET subjects:greater DAT availability may elevate threshold for dopamine action. Further behavioral andepigenetic characterizations of MAT-HETs, together with deeper characterization of maternal roles,could help to explore parent-of-origin mechanisms for such a peculiar phenotype.
Original languageEnglish
Number of pages0
JournalNeuroscience
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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