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Haploinsufficiency of the Parkinson’s disease gene synaptojanin1 is associated with abnormal responses to psychomotor stimulants and mesolimbic dopamine signaling

Psychology

Haploinsufficiency of the Parkinson’s disease gene synaptojanin1 is associated with abnormal responses to psychomotor stimulants and mesolimbic dopamine signaling

J. I. Mejaes, J. Saenz, et al.

Explore the critical role of the synaptojanin-1 gene in dopamine-related disorders as researchers Jennifer I. Mejaes, Jacqueline Saenz, Chris O'Brien, Carina M. Pizzano, Ping-Yue Pan, and David J. Barker investigate the impact of SYNJ1 deficiencies on reward processing and motivated behavior in mice. Discover how these findings uncover abnormal mesolimbic dopamine signaling and the implications for therapeutic strategies.

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Playback language: English
Abstract
The synaptojanin-1 (*SYNJ1*) gene is crucial for dopamine-related disorders. *Synj1* deficient mice (*Synj1<sup>+/-</sup>*) show impaired dopaminergic synaptic vesicular recycling. This study investigated how *Synj1* deficits affect the mesolimbic system, reward processing, and motivated behavior in male and female *Synj1<sup>+/-</sup>* and *Synj1<sup>+/+</sup>* mice using behavioral tests. *Synj1<sup>+/-</sup>* mice showed normal reward processing and sucrose motivation. However, male *Synj1<sup>+/-</sup>* mice exhibited attenuated cocaine conditioned place preference, not attributable to spatial memory deficits. *Synj1<sup>+/-</sup>* mice showed delayed peak dopamine release after cocaine, with female mice also exhibiting slower dopamine decay linked to cocaine-induced DAT responses. These findings reveal abnormal mesolimbic DA signaling due to *SYNJ1* deficiencies, highlighting the need for therapeutics to restore DAT function.
Publisher
Frontiers in Behavioral Neuroscience
Published On
Authors
Jennifer I. Mejaes, Jacqueline Saenz, Chris O'Brien, Carina M. Pizzano, Ping-Yue Pan, David J. Barker
Tags
SYNJ1
dopamine
reward processing
motivated behavior
cocaine
mesolimbic system
synaptic vesicular recycling
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