Former Training Relieves the Later Development of Behavioral Inflexibility in an Animal Model Overexpressing the Dopamine Transporter

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

A range of dopamine-dominating neuropsychiatric disorders present with cognitive deficits. In accordance, the dopamine transporter overexpressing rat model (DAT-tg rat) displays cognitive deficits by means of behavioral inflexibility and learning disabilities. It remains to be investigated when cognitive deficits emerge, due to the inherent DA irregularities, during the life course of the DAT-tg rat and what may relieve symptoms. The Morris water maze (MWM) was used to assess cognitive abilities in three cohorts of DAT-tg rats. In the first cohort, the development of cognitive deficits was assessed by repeatedly testing animals in the MWM at postnatal day (PND) 35, 60, and 90. In the second and third cohort, pharmacological interventions and transcranial direct current stimulation (tDCS) were tested in adult animals to understand what drives, and thus relieves, the deficits. Minor differences were observed between DAT-tg rats and control rats at PND 35 and 60, whereas cognitive deficits fully emerged at PND 90. A high dosage of methylphenidate diminished both behavioral inflexibility and improved learning abilities in adult rats. Interestingly, rats subjected early in life to the MWM also displayed improved behavioral flexibility as compared to rats naïve to the paradigm. Cognitive deficits gradually develop over time and fully emerge in adulthood. Pharmacological modulation of the ubiquitous DAT overexpression overall improves deficits in adult rats, whereas early training decreases later development of behavioral inflexibility. Thus, former training may constitute a preventive avenue that alters some aspects of cognitive deficits resulting from inherent DA abnormalities.

Details

OriginalspracheEnglisch
Seiten (von - bis)7182-7193
Seitenumfang12
FachzeitschriftMolecular neurobiology
Jahrgang59
Ausgabenummer12
PublikationsstatusVeröffentlicht - 20 Sep. 2022
Peer-Review-StatusJa

Externe IDs

Scopus 85138406759
PubMed 36125729
Mendeley e2ecb91a-0271-3236-b74d-c41ddf9179fc
unpaywall 10.1007/s12035-022-03029-5
WOS 000855605900001

Schlagworte

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Schlagwörter

  • Animal model, Cognitive deficits, Dopamine irregularities, Transcranial Direct Current Stimulation, Animals, Dopamine, Maze Learning/physiology, Rats, Methylphenidate/pharmacology, Dopamine Plasma Membrane Transport Proteins, Disease Models, Animal, CAUDATE-PUTAMEN, RECEPTOR, WATER MAZE, MEDIAL PREFRONTAL CORTEX, NEURONS, SPATIAL WORKING-MEMORY, METHYLPHENIDATE, SYSTEMS, STRIATUM, EXPOSURE