The Lack of Dopamine Transporter Is Associated With Conditional Associative Learning Impairments and Striatal Proteomic Changes

• DOI: 10.3389/fpsyt.2022.799433
• Publication Date: 2022-03-18T05:25:56Z
• Authors: Artem Savchenko; Carina Müller; Jana Lubec; Damiana Leo; Volker Korz; Leila Afjehi-Sadat; Jovana Malikovic; Fernando J. Sialana; Gert Lubec; Ilya Sukhanov
• Keywords: Associative learning; Incentive salience

Dopamine (DA) is critically involved in different functions of the central nervous system (CNS) including control voluntary movement, affect, reward, sleep, and cognition. One key components DA neurotransmission reuptake by transporter (DAT), ensuring rapid clearance from synaptic cleft. Thus, lack DAT leads to persistent high extracellular levels. While there strong evidence for a role striatal dopaminergic activity learning memory processes, little known about contribution deficiency conditional impairments underlying molecular processes. DAT-knockout (DAT-KO) rats were tested set behavioral experiments evaluating associative learning, which requires unaltered function. In parallel, large-scale proteomic analysis striatum was performed identify factors probably patterns. DAT-KO incapable acquire new operant skill Pavlovian/instrumental autoshaping, although stimulus-unconditional stimulus (CS-US) association seems be unaffected. These findings suggest that directly or indirectly contributes reduction transference incentive salience reward CS. We propose specific impairment might caused adaptations hyperdopaminergic state, presumably dopamine receptor 1 (DRD1) hypofunction, as proposed analysis. Whether DRD1 downregulation can cause cognitive deficits state subject discussion, further studies are needed answer this question. This study may useful interpretation previous design future field.