Related Experiment Video
Updated: May 23, 2026
Animal Models of Depression - Chronic Despair Model (CDM)
Published on: September 23, 2021
Exofocal dopaminergic degeneration as antidepressant target in mouse model of poststroke depression
Golo Kronenberg1, Mustafa Balkaya, Vincent Prinz
1Klinik und Poliklinik für Neurologie, Charité-Universitätsmedizin Berlin, Germany; Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Background:
Although poststroke depression (PSD) is a frequent chronic complication of stroke with high relevance for outcome and survival, underlying pathomechanisms remain inadequately understood. This may be because suitable animal models are largely lacking and existing models are poorly characterized.
Methods:
Male 129/SV mice were subjected to 30-min middle cerebral artery occlusion (MCAo)/reperfusion and serial magnetic resonance imaging scans. A subset of animals received selective serotonin reuptake inhibitor citalopram starting 7 days after MCAo. Behavioral assessment was performed at 14 weeks. To identify biological correlates of PSD, we quantified corticosterone levels in serum and brain-derived neurotrophic factor levels in brain. The integrity of the mesolimbic dopaminergic system was assessed using tyrosine hydroxylase and dynorphin in situ hybridizations as well as dopamine transporter autoradiography.
Results:
Left, but not right, MCAo, elicited anhedonia and increased anxiety and despair. This depression-like syndrome was associated with alterations in the mesolimbic reward system. MCAo resulted in delayed degeneration of dopaminergic neurons in ipsilateral midbrain, which was accompanied by reduced dopamine concentrations and decreased levels of dopamine transporter density along with increased brain-derived neurotrophic factor protein levels in ischemic striatum and increased dynorphin messenger RNA expression in nucleus accumbens. Chronic antidepressant treatment initiated as late as 7 days after stroke reversed the behavioral phenotype, prevented degeneration of dopaminergic midbrain neurons, and attenuated striatal atrophy at 4 months.
Conclusions:
Our results highlight the importance of the dopaminergic system for the development of PSD. Prevention of secondary neurodegeneration by antidepressants may provide a novel target for subacute stroke therapy.
Insights
Poststroke depression (PSD) in mice involves the dopaminergic system and can be treated with antidepressants. Early antidepressant intervention may prevent neurodegeneration and improve outcomes after stroke.
Area of Science:
- Neuroscience
- Pharmacology
- Stroke Research
Background:
- Poststroke depression (PSD) is a common complication impacting stroke outcomes.
- Underlying mechanisms of PSD are poorly understood due to a lack of suitable animal models.
Purpose of the Study:
- To investigate the pathomechanisms of PSD using a mouse model.
- To assess the therapeutic potential of antidepressants in treating PSD and associated neurodegeneration.
Main Methods:
- Middle cerebral artery occlusion (MCAo) model in mice.
- Behavioral assessments for depression-like symptoms.
- Analysis of dopaminergic system integrity and neurotrophic factors.
- Treatment with citalopram, a selective serotonin reuptake inhibitor.
Main Results:
- MCAo induced depression-like behaviors (anhedonia, anxiety, despair) linked to mesolimbic reward system alterations.
- Stroke caused delayed dopaminergic neuron degeneration, reduced dopamine, and altered transporter/receptor expression.
- Antidepressant treatment initiated 7 days post-stroke reversed behavioral deficits and prevented neuronal loss.
Conclusions:
- The dopaminergic system is crucial in the development of PSD.
- Antidepressants may offer a novel therapeutic strategy for subacute stroke by preventing secondary neurodegeneration.
