Single-electrode simultaneous detection of tonic dopamine and serotonin in vivo using an interleaved cyclic square wave voltammetry approach

초록

Tonic levels of DA and 5-HT serve as master regulators of motivational behavior and affective stability, yet their simultaneous quantification in vivo has remained a significant technical challenge. Here, we present an interleaved scanning strategy that alternates between Multiple Cyclic Square Wave Voltammetry (MCSWV) and N-shaped Multiple Cyclic Square Wave Voltammetry (N-MCSWV) waveforms on a single carbon fiber microelectrode, enabling the concurrent measurement of absolute basal concentrations of both neurotransmitters. Systematic optimization of repetition time and holding potential confirmed that the interleaved approach fully preserves the sensitivity and selectivity of each individual waveform. A two-step mathematical deconvolution algorithm, exploiting the inherent 5-HT selectivity of N-MCSWV, was established to precisely isolate the DA contribution from the composite MCSWV signal. In vitro validation demonstrated excellent linearity and selectivity against key metabolic interferents, including DOPAC and 5-HIAA. Pharmacological challenges in the NAc of anesthetized rats further confirmed the in vivo efficacy of the platform: escitalopram selectively elevated tonic 5-HT to 171.1% of baseline while leaving DA unchanged, whereas pargyline concurrently increased both tonic DA (120.4%) and 5-HT (116.1%). These findings demonstrate that interleaved scanning is a robust, high-resolution tool for simultaneously monitoring complex monoaminergic interactions, offering a powerful platform for advancing our understanding of the neurochemical basis of reward and emotional regulation.

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