Prelimbic Stimulation Ameliorates Depressive-Like Behaviors and Increases Regional BDNF Expression in a Novel Drug-Resistant Animal Model of Depression

Moshe, Hagar; Gal, Ram; Barnea‐Ygael, Noam; Gulevsky, Tatiana; Alyagon, Uri; Zangen, Abraham

doi:10.1016/j.brs.2015.10.009

Cited by 30 publications

(19 citation statements)

References 64 publications

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“…Control rats were kept for 4 weeks without any treatment. The success of the CMS was verified by the sucrose preference test, as previously described, by measuring the percent consumption of 0.2% sucrose solution out of total liquids (rats were given free access to water and the sucrose solution) during 2 weeks (Figure ).…”

Section: Methodsmentioning

confidence: 99%

“…Animals from the genetic model developed in our lab were selectively bred according to measurements of three separate behavioral tests for depression, as detailed in Gersner et al and Moshe et al Briefly, rats from each generation were challenged with the FST, the sucrose preference test, and home‐cage locomotion. The FST was performed in a custom‐built cylindrical water tank, where rats were placed in the water for 10 minutes, and their behavior was video recorded and analyzed with a custom‐built algorithm as described previously to produce the mobility score.…”

Section: Methodsmentioning

confidence: 99%

“…Production of tissue proteins was performed as previously described . Briefly, rats were decapitated 3 days after the relapse test and their brains were extracted, frozen immediately in isopropanol on dry ice, and stored at −80°C.…”

Section: Methodsmentioning

confidence: 99%

“…Here, we investigated the effects of depressive‐like states on different stages of cocaine SA in the conflict model. Depressed‐like states were induced through the common model of chronic‐mild stress (CMS), and by selective breeding of our genetic model termed depressed rat line (DRL) . The DRL model was produced through a multifactorial selective breeding procedure based on three independent measures of core depressed‐like behaviors.…”

Section: Introductionmentioning

confidence: 99%

“…The DRL model was produced through a multifactorial selective breeding procedure based on three independent measures of core depressed‐like behaviors. DRL rats display several behavioral and neurochemical alterations found in other validated models for depression, including reduced sucrose preference, reduced immobility in the forced swim test (FST), decreased exploration in the open field test and reduced BDNF levels in the dorsal hippocampus . Importantly, the two depression models differ in their response to antidepressant treatments: while the effects of CMS are restored by both antidepressant medications and electroconvulsive therapy (ECT) , DRL rats respond only to ECT.…”

Section: Introductionmentioning

confidence: 99%

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Increased relapse to cocaine‐seeking in a genetic model for depression

et al. 2019

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The greatest difficulty in treating cocaine addiction is the enormous rates of relapse, which occur despite immense negative consequences. Relapse risks are even greater in addicts with comorbid depression, perhaps because they use drugs to alleviate depressive symptoms. Only a few preclinical studies have examined this comorbidity, mostly exploring depressive-like effects following drug exposure. We examined rats from two different depression-like models: (a) chronic-mild-stress (CMS), which respond to antidepressant medications and (b) depressed-rat-line (DRL), a genetic model of selective breeding, which is less responsive to antidepressant medications.We tested addictive behaviors in a cocaine self-administration procedure, including the "conflict model," where drug-seeking and relapse encounter adverse consequences: an electrified grid in front of the drug-delivering lever. Following behavioral testing, we explored a potential association between behavioral outcomes and protein expression of brain-derived neurotrophic factor (BDNF). We found that DRL rats self-administer more cocaine compared with both CMS and controls, while CMS and control groups did not differ significantly. Notably, DRL but not CMS rats, displayed higher rates of relapse than controls, and expressed higher levels of BDNF in the prelimbic cortex (PLC). Potential translation of these results suggest that medication-resistant depressed patients tend to consume more drugs and are more susceptible to relapse. The increase in PLC BDNF levels is consistent with previous rat models of depression, and concomitantly, with its suggested role in promoting cocaine-seeking.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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