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

Rummel, Julia; Voget, Mareike; Hadar, Ravit; Ewing, Samuel G.; Sohr, Reinhard; Klein, Julia; Sartorius, Alexander; Heinz, Andreas; Mathé, Aleksander A.; Vollmayr, Barbara; Winter, Christine

doi:10.1016/j.jpsychires.2016.06.016

Cited by 33 publications

(10 citation statements)

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“…43 Neurochemical effects of mPFC-DBS have so far been described for the Hipp and Nacc; in vivo measurements via microdialysis revealed increments of serotonergic transmission in both projection sites as a consequence of mPFC-DBS. 45,47 Together these findings imply that the remarkable behavioral effectiveness of early mPFC-DBS could be related to an early interference of PFC-neuromodulation with the maldevelopment of dopaminergic and serotonergic transmission in the mPFC, Hipp and GP.…”

Section: Discussionmentioning

confidence: 92%

Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia

et al. 2017

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The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia's neurodevelopmental course. We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive neuromodulation approaches may be a viable preventive strategy.

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Section: Discussionmentioning

confidence: 92%

Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia

et al. 2017

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“…In FR or PR operant tasks, STN-DBS consistently decreased intravenous self-administration of addictive drugs (Rouaud et al, 2010;Wade et al, 2017). And while the effects of STN-DBS on motivation for natural rewards is more heterogeneous, the predominant effect of STN-DBS is also a decrease in rewards earned and consumed (Rummel et al, 2016) (Vachez et al, 2020b), but see (Rouaud et al, 2010;Vachez et al, 2020a). A decrease in reward seeking was also evident in extinction tasks, i.e., where STN-DBS operant responses were decreased in the absence of a previously available food pellet (Klavir et al, 2009).…”

Section: Stn-dbs Decreases Reward Seekingmentioning

confidence: 95%

Deep Brain Stimulation of the Subthalamic Nucleus Modulates Reward-Related Behavior: A Systematic Review

Vachez

Creed

2020

Front. Hum. Neurosci.

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Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for the motor symptoms of movement disorders including Parkinson's Disease (PD). Despite its therapeutic benefits, STN-DBS has been associated with adverse effects on mood and cognition. Specifically, apathy, which is defined as a loss of motivation, has been reported to emerge or to worsen following STN-DBS. However, it is often challenging to disentangle the effects of STN-DBS per se from concurrent reduction of dopamine replacement therapy, from underlying PD pathology or from disease progression. To this end, pre-clinical models allow for the dissociation of each of these factors, and to establish neural substrates underlying the emergence of motivational symptoms following STN-DBS. Here, we performed a systematic analysis of rodent studies assessing the effects of STN-DBS on reward seeking, reward motivation and reward consumption across a variety of behavioral paradigms. We find that STN-DBS decreases reward seeking in the majority of experiments, and we outline how design of the behavioral task and DBS parameters can influence experimental outcomes. While an early hypothesis posited that DBS acts as a “functional lesion,” an analysis of lesions and inhibition of the STN revealed no consistent pattern on reward-related behavior. Thus, we discuss alternative mechanisms that could contribute to the amotivational effects of STN-DBS. We also argue that optogenetic-assisted circuit dissection could yield important insight into the effects of the STN on motivated behavior in health and disease. Understanding the mechanisms underlying the effects of STN-DBS on motivated behavior-will be critical for optimizing the clinical application of STN-DBS.

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“…Nevertheless, our animal model is representative of a particularly resistant kind of obesity, which could potentially benefit from NAcc-DBS depending on the genetic background. We selected the DBS parameters for three main reasons: the success obtained in previous approaches using bilateral DBS [ 23 , 24 ] and similar stimulation protocols [ 22 , 27 , 34 , 69 ]; the tolerance associated with continuous DBS treatments [ 70 , 71 ]; and the technical difficulties in obtaining portable rat stimulators in our facilities. Nevertheless, DBS protocols which were closer to the current clinical scenario may reveal larger differences in weight gain [ 22 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

“…Stimulation was applied for 1 hour/day over 15 days. These settings were chosen based on previous preclinical and clinical studies [ 25 , 33 , 34 ].…”

Section: Methodsmentioning

confidence: 99%

Stimulating the nucleus accumbens in obesity: A positron emission tomography study after deep brain stimulation in a rodent model

et al. 2018

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PurposeThe nucleus accumbens (NAcc) has been suggested as a possible target for deep brain stimulation (DBS) in the treatment of obesity. Our hypothesis was that NAcc-DBS would modulate brain regions related to reward and food intake regulation, consequently reducing the food intake and, finally, the weight gain. Therefore, we examined changes in brain glucose metabolism, weight gain and food intake after NAcc-DBS in a rat model of obesity.ProceduresElectrodes were bilaterally implanted in 2 groups of obese Zucker rats targeting the NAcc. One group received stimulation one hour daily during 15 days, while the other remained as control. Weight and daily consumption of food and water were everyday registered the days of stimulation, and twice per week during the following month. Positron emission tomography (PET) studies with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) were performed 1 day after the end of DBS. PET data was assessed by statistical parametric mapping (SPM12) software and region of interest (ROI) analyses.ResultsNAcc-DBS lead to increased metabolism in the cingulate-retrosplenial-parietal association cortices, and decreased metabolism in the NAcc, thalamic and pretectal nuclei. Furthermore, ROIs analyses confirmed these results by showing a significant striatal and thalamic hypometabolism, and a cortical hypermetabolic region. However, NAcc-DBS did not induce a decrease in either weight gain or food intake.ConclusionsNAcc-DBS led to changes in the metabolism of regions associated with cognitive and reward systems, whose impairment has been described in obesity.

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

Cited by 33 publications

References 70 publications

Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia

Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia

Deep Brain Stimulation of the Subthalamic Nucleus Modulates Reward-Related Behavior: A Systematic Review

Stimulating the nucleus accumbens in obesity: A positron emission tomography study after deep brain stimulation in a rodent model

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