Medial Forebrain Bundle Deep Brain Stimulation has Symptom-specific Anti-depressant Effects in Rats and as Opposed to Ventromedial Prefrontal Cortex Stimulation Interacts With the Reward System

Testing different paradigms to optimize antidepressant deep brain stimulation in different rat models of depression

“…We and others have previously reported elevated intracellular serotonin-content to constitute one of the pathophysiological characteristic of FSL rats (Voget et al, 2015) that is reduced upon successful antidepressant treatment (Zangen et al, 1997). Likewise, our present results show behaviorally effective DBS to decrease intracellular serotonin levels.…”

“…FSL and control rats were randomly divided into the following groups: sham-stimulation (with electrodes in the STN, Nacc, or vmPFC), STN-DBS, Nacc-DBS, and vmPFC-DBS ( Figure S1A) with electrodes implanted into the respective targets. One week after surgery chronic-intermittent DBS treatment, as usually performed in animal experimental setups (Hamani et al, 2010a,b;Rea et al, 2014;Edemann-Callesen et al, 2015) and behavioral testing began with 2-3 days in between tests. Sham groups were connected to the stimulation system, but received no DBS.…”

“…Open field test ( Rummel et al, 2016 9 for initial latency to immobility (Edemann-Callesen et al, 2015;Porsolt et al, 1978;Rea et al, 2014). The learned helplessness paradigm (LH) was conducted in operant conditioning boxes (Operant Behavior System Mannheim Type 259900, TSE, Bad Hamburg, Germany) and…”

“…Studies applying DBS in rats report antidepressant effects for DBS to the ventromedial prefrontal cortex (vmPFC, rodent analogue of Cg25, Hamani et al, 2010a,b;Rea et al, 2014), Nacc (Gersner et al, 2010), MFB (Edemann-Callesen et al, 2015), ventral tegmental area (VTA, Gazit et al, 2015) and lateral habenula (LHb, Meng et al, 2011). Most of these investigations however have been carried out in naïve rats or in single animal models of depression.…”

“…Distance traveled was scored using video tracking software (EthoVision XT 8.5, Noldus IT, Netherlands). Sucrose consumption test (SCT): The amount of sucrose solution (Milchmädchen, Nestlé, 1:3)consumed over a period of 15 min after food restriction was normalized to the individual body weight(Edemann-Callesen et al, 2015;Enkel et al, 2010;Rea et al, 2014). Forced swim test (FST): Rats were conditioned to water-filled glass cylinders (depth: 33 cm, 25° C) for 15 min followed by a 5 min test session 24 h thereafter.…”