Anti-Anhedonic Effect of Deep Brain Stimulation of the Prefrontal Cortex and the Dopaminergic Reward System in a Genetic Rat Model of Depression: An Intracranial Self-Stimulation Paradigm Study

• Main Authors: Ellis Rea, Julia Rummel, Timo T. Schmidt, Ravit Hadar, Andreas Heinz, Aleksander A. Mathé, Christine Winter
• Format: Article
• Language: English
• Published: Elsevier 2014-01-01
• Series: Brain Stimulation
• Subjects: Anhedonia; Deep brain stimulation; Flinders Sensitive Line; Intracranial self-stimulation; Major depression
• Online Access: http://www.sciencedirect.com/science/article/pii/S1935861X13002842

Background: One of the two core symptoms of major depression (MD), whether uni- or bipolar, is the inability to experience pleasure, suggested to be triggered by dysregulation within the brain reward system. In recent years, deep brain stimulation (DBS) has evolved as a potential tool to modulate pathological neural activity; stimulation of the subgenual cingulate (Cg25) has been shown to reduce depressive symptoms, including anhedonia. In rodents, the ventromedial prefrontal cortex (vmPFC) is likely to represent the correlate of Cg25 and accordingly, stimulation of vmPFC reduces anhedonia-like behavior in rats. Objective/hypothesis: The present study addresses the question of whether the anti-anhedonic effect of vmPFC-DBS is mediated by the brain reward system. Methods: Rats of the Flinders Sensitive Line (FSL), a validated genetic animal model of depression, and its controls, the Flinders Resistant Line (FRL), were stimulated in the vmPFC and tested in the forced swim test (FST), sucrose consumption test (SCT) and the intracranial self-stimulation (ICSS) paradigm. The curve-shift paradigm of ICSS was used in combination with vmPFC-DBS, d-amphetamine and fluoxetine to quantify reward-facilitating or -attenuating treatment effects. Results: Our findings support anti-depressive efficacy of vmPFC-DBS with respect to despair- and anhedonia-like behavior, as shown in the FST and SCT, respectively. However, DBS did not elicit reward-facilitating or reward-attenuating effects on ICSS behavior. Conclusion: These data suggest that it is unlikely that the anti-anhedonic effect of vmPFC-DBS depends on the mesolimbic dopaminergic reward system.