Induction of depressive-like behavior by intranigral 6-OHDA is directly correlated with deficits in striatal dopamine and hippocampal serotonin

Santiago, Ronise Martins; Barbiero, Janaína K.; Gradowski, Raisa W.; Bochen, Suelen; Lima, Marcelo M.S.; Cunha, Cláudio Da; Andreatini, Roberto; Vital, Maria A.B.F.

doi:10.1016/j.bbr.2013.10.035

Cited by 65 publications

(37 citation statements)

References 36 publications

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“…Locomotor activity in the open field not only depends on motor skills but also on the motivation to explore a novel arena (Sousa et al, 2006). In the present study, unilaterally lesioning the SNc caused striking impairments in horizontal and vertical activity of the rats, which are in good agreement with previous reports (Santiago et al, 2010(Santiago et al, , 2014Sourani et al, 2012). In both shamoperated and 6-OHDA-lesioned rats, intra-LHb injection of Ro60-0175 or/and SB242084 did not affect locomotor activity in the open field.…”

Section: Depressive-like Behaviors Involve Increased Firing Activity supporting

confidence: 94%

“…In the present study, rats with complete unilateral 6-OHDA lesions of the SNc showed decreased sucrose consumption in the sucrose preference test and increased immobility time in the FST compared to sham-operated rats, indicating the induction of depressive-like responses. Therefore, our results support previous investigations (Winter et al, 2007;Santiago et al, 2010Santiago et al, , 2014Sourani et al, 2012), and the notion that unilaterally lesioning the SNc in rat is able to induce depressive-like behaviors as common neuropsychiatric comorbidity of PD. Current data showed that the unilateral DA lesion reduced locomotor activity; however, we found that there was a strong tendency for the lesioned rats to be more immobile (depressive-like) in the FST than sham-operated rats, suggesting a depressive effect of DA depletion.…”

Section: Depressive-like Behaviors Involve Increased Burst-firing Actsupporting

confidence: 93%

“…Although depression is a common non-motor symptom in PD, previous studies into depressive-like behaviors in different rat models of PD were less consistent (Winter et al, 2007;Branchi et al, 2008;Tadaiesky et al, 2008;Eskow Jaunarajs et al, 2010Santiago et al, 2010Santiago et al, , 2014Zhang et al, 2011;Delaville et al, 2012;Sourani et al, 2012;Carvalho et al, 2013;Hui et al, 2014). The discrepancy could be related to the site of 6-OHDA injection, the extent of DA depletion, unilateral or bilateral lesions, used depression paradigms and time frame for the behavior tests.…”

Section: Depressive-like Behaviors Involve Increased Burst-firing Actmentioning

confidence: 82%

“…Previous studies into depressive-like behaviors in 6-hydroxydopamine (6-OHDA)-lesioned rats have been limited and divergent. These studies reported increased or unchanged depressive-like behaviors in different 6-OHDA rat models of PD (Winter et al, 2007;Branchi et al, 2008;Tadaiesky et al, 2008;Eskow Jaunarajs et al, 2010Santiago et al, 2010Santiago et al, , 2014Zhang et al, 2011;Delaville et al, 2012;Sourani et al, 2012;Carvalho et al, 2013;Hui et al, 2014). Further, a dysfunctional 5-HT system is generally regarded as a risk factor for depression, and accumulating lines of evidences also suggest that degeneration of the nigrostriatal pathway leads to an impairment of 5-HT system, with evidence including the loss of 5-HT neurons, reduction of brain 5-HT content, hyperactivity of 5-HT neurons and alterations in various types of 5-HT receptors (Scholtissen et al, 2006;Wang et al, 2009;Huot et al, 2011).…”

Section: Introductionmentioning

confidence: 94%

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Activation of serotonin2C receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat

Han

Zhang

et al. 2015

Neuropharmacology

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Section: Depressive-like Behaviors Involve Increased Firing Activity supporting

confidence: 94%

Section: Depressive-like Behaviors Involve Increased Burst-firing Actsupporting

confidence: 93%

Section: Depressive-like Behaviors Involve Increased Burst-firing Actmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 94%

See 2 more Smart Citations

Activation of serotonin2C receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat

Han

Zhang

et al. 2015

Neuropharmacology

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“…The distance of center and periphery area were listed by the computer. After the observation period, the total travel distance in the arena of the OFT was counted (Santiago et al, 2014). …”

Section: Methodsmentioning

confidence: 99%

Adulthood Exposure to Lipopolysaccharide Exacerbates the Neurotoxic and Inflammatory Effects of Rotenone in the Substantia Nigra

Huang

Zhu

et al. 2017

Front. Mol. Neurosci.

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Parkinson’s disease (PD) is the second most neurodegenerative disorder with a regional decrease of dopamine (DA) neurons in the substantia nigra (SN). Despite intense exploration, the etiology of PD progressive process remains unclear. This study was to investigate the synergistic effects of systemic inflammation of lipopolysaccharide (LPS) and neurotoxicity of rotenone (ROT) on exacerbating DA neuron lesion. Male SD adulthood rats received a single intraperitoneal injection of LPS. Seven months later, rats were subcutaneously given ROT five times a week for consecutive 4 weeks. Rat behavior changes were assessed via rotarod and open-field tests. Brain SN was immunostained to evaluate DA neuronal loss and microglia activation. Striatum DA and its metabolites levels were determined by high performance liquid chromatography (HPLC) coupled with electrochemistry. The protein levels of α-synuclein (α-Syn), inflammatory factors and mitogen-activated protein kinase (MAPK) pathway activation were detected by western blotting analysis. Results indicated that no significant difference between the control and LPS alone groups was shown. Compared with ROT alone group, LPS combined with ROT significantly reduced motor activity and induced SN DA neurons loss accompanied by the decreased contents of striatum DA and its metabolites. Furthermore, LPS together with ROT enhanced microglia activation and the increased expressions of α-Syn and inflammatory factors and also MAPK signaling pathway activation. However, LPS alone had no significant effects on the above parameters. These findings suggest that adulthood exposure to LPS exacerbates the neurotoxic and inflammatory effects of ROT in the SN.

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Characterization of a new low‐dose 6‐hydroxydopamine model of Parkinson's disease in rat

Penttinen

Suleymanova

Albert

et al. 2016

J of Neuroscience Research

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Intrastriatal administration of 6-hydroxydopamine (6-OHDA) induces partial degeneration of the nigrostriatal pathway, mimicking the pathology of Parkinson's disease (PD). Setting up the partial lesion model can be challenging because a number of experimental settings can be altered. This study compares seven experimental settings in a single study on d-amphetamine-induced rotations, tyrosine hydroxylase (TH)-positive neurites in the striatum, dopamine transporter (DAT)-positive neurites in the striatum, and TH-positive cells in the substantia nigra pars compacta (SNpc) in rats. Moreover, we validate a new algorithm for estimating the number of TH-positive cells. We show that the behavior and immunoreactivity vary greatly depending on the injection settings, and we categorize the lesions as progressive, stable, or regressive based on d-amphetamine-induced rotations. The rotation behavior correlated with the degree of the lesion, analyzed by immunohistochemistry; the largest lesions were in the progressive group, and the smallest lesions were in the regressive group. We establish a new low-dose partial 6-OHDA lesion model in which a total of 6 μg was distributed evenly to three sites in the striatum at a 10° angle. The administration of low-dose 6-OHDA produced stable and reliable rotation behavior and induced partial loss of striatal TH-positive and DAT-positive neurites and TH-positive cells in the SNpc. This model is highly suitable for neurorestoration studies in the search for new therapies for PD, and the new algorithm increases the efficacy for estimating the number of dopamine neurons. This study can be extremely useful for laboratories setting up the partial 6-OHDA model.

show abstract

Induction of depressive-like behavior by intranigral 6-OHDA is directly correlated with deficits in striatal dopamine and hippocampal serotonin

Cited by 65 publications

References 36 publications

Activation of serotonin2C receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat

Activation of serotonin2C receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat

Adulthood Exposure to Lipopolysaccharide Exacerbates the Neurotoxic and Inflammatory Effects of Rotenone in the Substantia Nigra

Characterization of a new low‐dose 6‐hydroxydopamine model of Parkinson's disease in rat

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