Long‐term stability and characteristics of behavioral, biochemical, and molecular markers of three different rodent models for depression

Zhu, Han; Tao, Yanlin; Wang, Tingting; Zhou, Jin; Yang, Youxin; Cheng, Lin; Zhu, Huaqiang; Zhang, Weiqi; Huang, Fei; Wu, Xiaojun

doi:10.1002/brb3.1508

Cited by 22 publications

(14 citation statements)

References 55 publications

(62 reference statements)

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“…These results suggest that in our study, the hyperactivity observed in the OFT did not affect the FST behavior test. The lack of effect in the FST is consistent with other studies in OBX animals ( Zhu et al, 2020 ), although other authors have found an increase in the immobility in this test ( Morales-Medina et al, 2017 ). The variability in this test indicates that the FST is not a representative behavioral domain in the OBX model ( Alcantara et al, 2017 ).…”

Section: Discussionsupporting

confidence: 92%

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Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression

Flores-Burgess

Millón

Gago

et al. 2021

International Journal of Neuropsychopharmacology

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Background Selective serotonergic reuptake inhibitors, including fluoxetine (FLX), are the most commonly used for the treatment of major depression. However, they are only effective for remission in 30% of patients. Recently we observed that Galanin (1-15) [GAL(1-15)] enhanced the antidepressant effects of FLX in naïve animals suggesting a new augmentation strategy in depression. Methods We have analyzed in an animal model of depression, the olfactory bulbectomy (OBX) rats the effect of GAL(1–15) on FLX-mediated responses in the forced swimming test (FST) and in sucrose preference test (SPT) and the involvement of GALR2 with its antagonist M871. We have also studied the corticosterone levels in OBX after the coadministration of GAL(1-15) with FLX. Moreover, we studied whether the effects of GAL(1–15) on FLX actions were mediated via 5-HT1AR analyzing the binding characteristics, mRNA levels and the functionality of 5-HT1AR in the dorsal hippocampus. Results GAL(1-15) enhances the antidepressant-like effects induced by FLX in OBX animals in the FST and in the SPT. The involvement of the GALR2 was demonstrated with M871. Importantly, the mechanism underlying the GAL(1-15)/FLX interactions in the OBX animals involves the 5-HT1AR in the hippocampus at the plasma membrane (increase of affinity and density of 5HT1AR in the DG) and transcriptional (increase of 5HT1AR mRNA levels in DG and CA1) levels. Besides, the coadministration of GAL(1-15) and FLX also reduced OBX-increased corticosterone levels Conclusions The results open up the possibility to use GAL(1-15) in combination with FLX as a novel strategy for the treatment of depression.

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Section: Discussionsupporting

confidence: 92%

“…On the other hand, in the SPT that detects an anhedonia-like condition, which is a core feature of major depression and characteristic of the OBX model ( Millón et al, 2019 ; Zhou et al, 2019 ), we observed increased anhedonia ( Zhu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 52%

Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression

Flores-Burgess

Millón

Gago

et al. 2021

International Journal of Neuropsychopharmacology

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“…These results suggest that in our study, the hyperactivity observed in the open field test (OFT) is not affecting the FST or the TST behaviour test. The lack of effect in the FST is consistent with other studies in OBX animals [ 39 ] although other authors have found an increased in the immobility in this test [ 27 ]. This variability observed in this test indicates that the FST is not a representative behavioural domain in the OBX model [ 32 ].…”

Section: Discussionsupporting

confidence: 92%

Galanin(1-15) Potentiates the Antidepressant-like Effects Induced by Escitalopram in a Rat Model of Depression

García-Durán

Flores-Burgess

Cantero-García

et al. 2021

IJMS

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Selective 5-HT reuptake inhibitor antidepressants (SSRIs) are the first choice in major depressive disorder (MDD), but 50% of affected patients do not show improvement. Galanin(1-15) [GAL(1-15)] enhanced Fluoxetine antidepressant-like effects in an animal model of depression, the olfactory bulbectomy (OBX); however, further detailed analysis of GAL(1-15) effects as augmentation treatment in OBX rats are needed. In OBX rats, we analysed the effect of GAL(1–15) on Escitalopram (ESC)-mediated responses in behavioural tests related to despair. We studied whether GAL(1–15) effects involved 5-HT1AR using an in vivo model siRNA 5-HT1A knockdown rats. Moreover, we analysed by immunohistochemistry the expression of the immediate-early gene c-Fos (c-Fos IR) after the administration of GAL(1-15)+ESC in OBX rats in several nuclei involved in MDD. GAL(1-15) enhances the antidepressant-like effects of ESC, and the GALR2 antagonist M871 blocked GAL(1-15) mediated actions. The downregulation of 5-HT1AR by siRNA was sufficient to block GAL(1-15) effects. Our immunohistochemistry and principal component analysis (PCA) analysis suggest that two functional networks are involved in these effects; one includes the lateral (LHb) and medial (mHb) habenula, dorsal raphe (DR) and ventral tegmental area (VTA), and the other consists of the dentate gyrus (DG), and prefrontal cortex (PFC). The results open up the possibility of using GAL(1-15) in combination with SSRIs as a novel strategy for treating MDD.

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“…Similar to the previous studies (25,26), from PND28, pups received one of nine trials ( Table 1) every day until the end of the whole study (PND61). Each trial was randomly taken every day, and the same trial was not used twice in a row.…”

Section: Chronic Unpredictable Mild Stress (Cums)mentioning

confidence: 93%

The Effect of Early Maternal Separation Combined With Adolescent Chronic Unpredictable Mild Stress on Behavior and Synaptic Plasticity in Adult Female Rats

Huang

Shen

et al. 2021

Front. Psychiatry

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Our aims were to evaluate the depression model of early maternal separation (MS) combined with adolescent chronic unpredictable mild stress (CUMS) in female adult SD rats to observe the behavior and the expressions of synaptic proteins in rats and to provide a reference for the screening of antidepressant drug activity. In our study, MS and CUMS were conducted to establish a dual stress model on female rats. Behavioral tests, including the sucrose preference test, open field test, and zero maze test, were used to detect depression-like and anxiety-like behavior of animals. Nissl staining was used to detect the number of neuronal cells in the hippocampus CA1 and DG regions of rats from each group. Synaptophysin (SYN), postsynaptic density-95 (PSD-95), and growth-associated protein-43 (GAP-43) expressions in the hippocampus were detected by western blot. Expression of the hippocampus SYN protein was further detected by immunohistochemistry. Rats in the MS+CUMS group presented more serious depression-like and anxiety-like behavior than in the MS group. Also, few Nissl bodies in the hippocampus CA1 and DG regions, less percentage of SYN-positive cells, and downregulated expressions of SYN, PSD-95, and GAP43 were found in the hippocampus of rats in MS+CUMS group. In conclusion, adult female rats that underwent MS and CUMS performed more critical depression-like and anxiety-like behaviors, and this process may be resulted from synaptic plasticity impairment.

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Long‐term stability and characteristics of behavioral, biochemical, and molecular markers of three different rodent models for depression

Cited by 22 publications

References 55 publications

Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression

Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression

Galanin(1-15) Potentiates the Antidepressant-like Effects Induced by Escitalopram in a Rat Model of Depression

The Effect of Early Maternal Separation Combined With Adolescent Chronic Unpredictable Mild Stress on Behavior and Synaptic Plasticity in Adult Female Rats

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