title: Induction of depressive-like behavior by intranigral 6-OHDA is directly correlated with deficits in striatal dopamine and hippocampal serotonin.
abstract: 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.
authors.affiliation: Pharmacology Department, Federal University of Paraná, Brazil.
authors.forename: Ronise M
authors.initials: RM
authors.lastname: Santiago
authors.affiliation: Pharmacology Department, Federal University of Paraná, Brazil.
authors.forename: Janaína
authors.initials: J
authors.lastname: Barbiero
authors.affiliation: Pharmacology Department, Federal University of Paraná, Brazil.
authors.forename: Raisa W
authors.initials: RW
authors.lastname: Gradowski
authors.affiliation: Pharmacology Department, Federal University of Paraná, Brazil.
authors.forename: Suelen
authors.initials: S
authors.lastname: Bochen
authors.affiliation: Physiology Department, Federal University of Paraná, Brazil.
authors.forename: Marcelo M S
authors.initials: MM
authors.lastname: Lima
authors.affiliation: Pharmacology Department, Federal University of Paraná, Brazil.
authors.forename: Cláudio
authors.initials: C
authors.lastname: Da Cunha
authors.affiliation: Pharmacology Department, Federal University of Paraná, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Andreatini
authors.affiliation: Pharmacology Department, Federal University of Paraná, Brazil. Electronic address: vital@ufpr.br.
authors.forename: Maria A B F
authors.initials: MA
authors.lastname: Vital
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003863:Depression / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D018663:Adrenergic Agents; D013549:Sweetening Agents; D012701:Serotonin; D013395:Sucrose; D016627:Oxidopamine; D004298:Dopamine
keywords: 6-OHDA; Depressive-like behavior; Parkinson's disease