Spatiotemporal characterization of corticolimbic dopamine and noradrenaline signaling and affective state modulation by mfb stimulation

Background: Deep brain stimulation of the medial forebrain bundle (mfb DBS) is a promising intervention for psychiatric disorders, but the neurochemical mechanisms underlying its effects remain incompletely understood. Methods: In adult Sprague Dawley rats, fiber photometry was used to monitor mfb-DBS evoked dopamine (DA) and noradrenaline (NA)-signaling in the nucleus accumbens (NAc) and prefrontal cortex (PFC), following different stimulation patterns, laterality conditions, and prolonged stimulation paradigms. Ultrasonic vocalizations (USVs) were recorded in parallel as a behavioral measure. Results: Bilateral stimulation robustly increased catecholaminergic signals relative to sham in both NAc and PFC. The magnitude and temporal profile of these responses depended more on stimulation pattern rather than on laterality, with long pulse-width generally evoking the largest responses and laterality producing no significant differences across the four recording groups. During 10 min bilateral stimulation, catecholaminergic signals increased rapidly and remained elevated throughout stimulation, with the clearest sustained effect observed in NAc DA. mfb DBS also increased USV calls and peak frequencies, whereas these behavioral changes showed no consistent region-specific correlation with catecholaminergic signal magnitude. Conclusions: mfb DBS recruits catecholaminergic signaling in a parameter-dependent and region specific manner and increases positive-affective USV output. These findings identify temporal patterning as an important determinant of downstream circuit engagement, whereas the relationship between acute USV responses and regional catecholamine signaling appears more complex.