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

•The intranigral infusion of 6-OHDA was able to promote a depressive-like behavior.•6-OHDA-lesioned rats exhibited a reduction in the levels of hippocampal serotonin and striatal dopamine.•Animals that received 6-OHDA showed a decrease in swimming time and consumption of sucrose.•There is a correlat...

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Published in:	Behavioural brain research Vol. 259; pp. 70 - 77
Main Authors:	Santiago, Ronise M., Barbiero, Janaína, Gradowski, Raisa W., Bochen, Suelen, Lima, Marcelo M.S., Da Cunha, Cláudio, Andreatini, Roberto, Vital, Maria A.B.F.
Format:	Journal Article
Language:	English
Published:	Shannon Elsevier B.V 01-02-2014 Elsevier
Subjects:	6-OHDA Adrenergic Agents - toxicity Adult and adolescent clinical studies Animals Biological and medical sciences Corpus Striatum - metabolism Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Depression Depression - chemically induced Depression - pathology Depressive-like behavior Disease Models, Animal Dopamine - metabolism Exploratory Behavior - drug effects Food Preferences - drug effects Hippocampus - metabolism Male Medical sciences Mood disorders Neurology Neurons - metabolism Neurons - pathology Oxidopamine - toxicity Parkinson's disease Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Rats Rats, Wistar Serotonin - metabolism Substantia Nigra - drug effects Sucrose - administration & dosage Sweetening Agents - administration & dosage Swimming - psychology Time Factors Depressive-like behavior 6-OHDA Parkinson's disease Mood disorder Nervous system diseases Dopamine Serotonin Induction Central nervous system Parkinson disease Depression Basal ganglion Corpus striatum Catecholamine Oxidopamine Encephalon Cerebral disorder Central nervous system disease Neurotransmitter Degenerative disease Behavior Hippocampus Extrapyramidal syndrome
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Summary:	•The intranigral infusion of 6-OHDA was able to promote a depressive-like behavior.•6-OHDA-lesioned rats exhibited a reduction in the levels of hippocampal serotonin and striatal dopamine.•Animals that received 6-OHDA showed a decrease in swimming time and consumption of sucrose.•There is a correlation between hippocampal serotonin and time swimming and sucrose consumption.•There is a correlation between striatal dopamine levels and immobility time in the forced swim test. Among the non-motor phenomena of Parkinson's disease (PD) are depressive symptoms, with a prevalence of 40–70%. The reason for this high prevalence is not yet clear. The basal ganglia receives dopamine (DA) inputs from the substantia nigra pars compacta (SNpc), which is known to be impaired in PD patients. The neurotransmitter deficiency hypothesis of PD considers that low serotonin (5-hydroxytryptamine [5-HT]) activity in the brain in PD patients is a risk factor for depression. We investigated whether DA depletion promoted by the neurotoxin 6-hydroxydopamine (6-OHDA) is able to induce depressive-like behavior and neurotransmitter alterations that are similar to those observed in PD. To test this hypothesis, we performed intranigral injections of 6-OHDA in male Wistar rats and conducted motor behavior, depressive-like behavior, histological, and neurochemical tests. After the motor recovery period, 6-OHDA was able to produce anhedonia and behavioral despair 7, 14, and 21 days after neurotoxin infusion. These altered behavioral responses were accompanied by reductions of striatal DA. Additionally, decreases in hippocampal 5-HT content were detected in the 6-OHDA group. Notably, correlations were found between 5-HT and DA levels and swimming, immobility, and sucrose preference. Our results indicate that 6-OHDA produced depressive-like behavior accompanied by striatal DA and hippocampal 5-HT reductions. Moreover, DA and 5-HT levels were strongly correlated with “emotional” impairments, suggesting the important participation of these neurotransmitters in anhedonia and behavioral despair after 6-OHDA-induced nigral lesions.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0166-4328 1872-7549
DOI:	10.1016/j.bbr.2013.10.035