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

Abstract：

:Deep brain stimulation (DBS) of several targets induces beneficial responses in approximately 60% of patients suffering from treatment-resistant depression (TRD). The remaining 40% indicate that these stimulation sites do not bear therapeutic relevance for all TRD patients and consequently DBS-targets should be selected according to individual symptom profiles. We here used two animal models of depression known to have different genetic backgrounds and behavioral responses: the therapy-responsive Flinders sensitive line (FSL) and the therapy-refractory congenitally learned helpless rats (cLH) to study symptom-specific DBS effects i) of different brain sites ii) at different stimulation parameters, and iii) at different expressions of the disease. Sham-stimulation/DBS was applied chronic-intermittently or chronic-continuously to either the ventromedial prefrontal cortex (vmPFC, rodent equivalent to subgenual cingulate), nucleus accumbens (Nacc) or subthalamic nucleus (STN), and effects were studied on different depression-associated behaviors, i.e. anhedonia, immobility/behavioral despair and learned helplessness. Biochemical substrates of behaviorally effective versus ineffective DBS were analyzed using in-vivo microdialysis and post-mortem high-performance liquid chromatography (HPLC). We found that i) vmPFC-DBS outperforms Nacc-DBS, ii) STN-DBS increases depressive states, iii) chronic-continuous DBS does not add benefits compared to chronic-intermittent DBS, iv) DBS-efficacy depends on the disease expression modeled and iv) antidepressant DBS is associated with an increase in serotonin turnover alongside site-specific reductions in serotonin contents. The reported limited effectiveness of vmPFC DBS suggests that future research may consider the specific disease expression, investigation of different DBS-targets and alternative parameter settings.

journal_name

J Psychiatr Res

journal_title

Journal of psychiatric research

authors

Rummel J,Voget M,Hadar R,Ewing S,Sohr R,Klein J,Sartorius A,Heinz A,Mathé AA,Vollmayr B,Winter C

doi

10.1016/j.jpsychires.2016.06.016

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

36-45

eissn

0022-3956

issn

1879-1379

pii

S0022-3956(16)30123-6

journal_volume

81

pub_type

杂志文章

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