Tonic Dopamine Sensing Reveals a D2/D3 Mediated Dopamine Response to Raclopride in ClockΔ19 Mice Model.

The circadian rhythm regulates physiological and behavioral processes, with disruptions linked to metabolic and neuropsychiatric disorders. Circadian genes play a crucial role in the regulation of dopaminergic signaling, yet the underlying molecular mechanisms remain unclear. This study investigates how the gene modulates dopamine (DA) dynamics using electrochemical DA sensing and molecular profiling. Utilizing carbon fiber electrodes (CFEs) with poly(3,4-ethylenedioxythiophene)/carbon nanotube (PEDOT/CNT) coatings, we measured extracellular DA levels in the striatum of wild-type (WT) and Δ19 mutant mice via square wave voltammetry (SWV). Pharmacological perturbation with raclopride (D2/D3 receptor antagonist) and nomifensine (dopamine reuptake inhibitor) revealed an increased DA receptor sensitivity in Δ19 mice, with a significantly faster DA response to raclopride. Molecular profiling via qRT-PCR showed elevated () expression in the ventral tegmental area (VTA) of Δ19 mice, suggesting increased DA synthesis. Additionally, Δ19 mice exhibited higher expression of D2 and D3 dopamine receptors and () in the VTA, implicating altered dopaminergic and γ-aminobutyric acid (GABA)ergic regulation. These findings highlight the gene's role in DA homeostasis, revealing its impact on neurotransmission.