Academic Journal
Effects of early postnatal dopamine transporter (DAT) inhibition on social and cognitive behavior in a rat model of autism.
| Τίτλος: | Effects of early postnatal dopamine transporter (DAT) inhibition on social and cognitive behavior in a rat model of autism. |
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| Συγγραφείς: | Gibula-Tarlowska E; Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin 20-093, Poland., Grochecki P; Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin 20-093, Poland., Lubinska J; Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin 20-093, Poland., Sliwa M; Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow 31-343, Poland., Smaga I; Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow 31-343, Poland., Marszalek-Grabska M; Department of Neurotoxicology, Institute of Rural Health, Lublin 20-090, Poland., Lubec G; Department of Neuroproteomics, Paracelsus Medical University, Salzburg 5020, Austria., Slowik T; Experimental Medicine Center, Medical University, Jaczewskiego 8, Lublin 20-090, Poland., Slotwinska W; Medical Faculty, Medical University of Lublin, Lublin 20-059, Poland., Kotlinski R; Clinical Department of Cardiac Surgery, University of Rzeszow, Rzeszow 35-301, Poland., Listos J; Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin 20-093, Poland., Kedzierska E; Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin 20-093, Poland., Filip M; Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow 31-343, Poland., Kotlinska JH; Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin 20-093, Poland. Electronic address: jolanta.kotlinska@umlub.edu.pl. |
| Πηγή: | Behavioural brain research [Behav Brain Res] 2026 Oct 02; Vol. 514, pp. 116400. Date of Electronic Publication: 2026 Jul 25. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 8004872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7549 (Electronic) Linking ISSN: 01664328 NLM ISO Abbreviation: Behav Brain Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press. |
| Ιατρικοί όροι (MeSH): | Dopamine Plasma Membrane Transport Proteins*/metabolism , Dopamine Plasma Membrane Transport Proteins*/antagonists & inhibitors , Cognition*/drug effects , Cognition*/physiology , Autistic Disorder*/metabolism , Behavior, Animal*/drug effects , Behavior, Animal*/physiology , Autism Spectrum Disorder*/metabolism , Autism Spectrum Disorder*/chemically induced , Social Behavior*, Prenatal Exposure Delayed Effects/metabolism ; Valproic Acid/pharmacology ; Brain-Derived Neurotrophic Factor/metabolism ; Brain/metabolism ; Brain/drug effects ; Dopamine Uptake Inhibitors/pharmacology ; Receptors, Dopamine D2/metabolism ; Animals ; Female ; Male ; Disease Models, Animal ; Rats, Wistar ; Pregnancy ; Rats ; Anxiety |
| Περίληψη: | Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social behavior and cognition. Increasing evidence suggests that alterations in dopaminergic neurotransmission, including changes in dopamine transporter (DAT) function, may contribute to ASD-related behavioral abnormalities. This study investigated whether selective DAT inhibition during early postnatal development influences behavioral and molecular alterations in a rat model of ASD induced by prenatal exposure to sodium valproate (NaVP). Pregnant Wistar rats received NaVP (600 mg/kg, i.p.) on gestational day 12.5. Male offspring were treated with the selective DAT inhibitor CE-123 (10 mg/kg, i.p.) once daily from postnatal day (PND) 10-23. Behavioral assessments during adolescence (PND25-42) evaluated social interaction, recognition memory, spatial preference, anxiety-like behavior, locomotor activity, and aversive memory. DAT, dopamine D2 receptor, brain-derived neurotrophic factor (BDNF), and interleukin-1β (IL-1β) protein expression were assessed in selected brain regions. Prenatal NaVP exposure impaired social novelty discrimination, declarative, spatial, and aversive memory, reduced locomotor activity, and increased anxiety-like behavior. These behavioral alterations were accompanied by elevated DAT and dopamine D2 receptor expression. Early postnatal CE-123 treatment attenuated several ASD-like behavioral abnormalities, normalized DAT and dopamine D2 receptor expression, increased BDNF levels in the prefrontal cortex (PFC), and increased IL-1β expression, without inducing non-specific locomotor stimulation. Together, these findings demonstrate that early postnatal CE-123 treatment was associated with long-lasting behavioral improvements accompanied by alterations in dopaminergic markers and BDNF expression. Although these findings support a role for dopaminergic regulation and neuroplasticity in the observed behavioral effects, the underlying mechanisms require further investigation. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Autism spectrum disorder; CE-123; Cognition; Dopamine D2 receptor; Dopamine transporter; Sodium valproate |
| Substance Nomenclature: | 0 (Dopamine Plasma Membrane Transport Proteins) 614OI1Z5WI (Valproic Acid) 0 (Brain-Derived Neurotrophic Factor) 0 (Dopamine Uptake Inhibitors) 0 (Receptors, Dopamine D2) |
| Entry Date(s): | Date Created: 20260725 Date Completed: 20260812 Latest Revision: 20260812 |
| Update Code: | 20260813 |
| DOI: | 10.1016/j.bbr.2026.116400 |
| PMID: | 42501761 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1872-7549 |
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| DOI: | 10.1016/j.bbr.2026.116400 |