Depressive-like behaviors alterations induced by intranigral MPTP, 6-OHDA, LPS and rotenone models of Parkinson's disease are predominantly associated with serotonin and dopamine.
Depression is a frequently encountered non-motor feature of Parkinson's disease (PD) and it can have a significant impact on patient's quality of life. Considering the differential pathophysiology of depression in PD, it prompts the idea that a degenerated nigrostriatal system plays a role in depressive-like behaviors, whilst animal models of PD are employed. Therefore, we addressed the question of whether dopamine (DA) depletion, promoted by the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), lipopolysaccharide (LPS) and rotenone are able to induce depressive-like behaviors and neurotransmitters alterations similarly that encountered in PD. To test this rationale, we performed intranigral injections of each neurotoxin, followed by motor behavior, depressive-like behaviors, histological and neurochemical tests. After the motor recovery period, MPTP, 6-OHDA and rotenone were able to produce anhedonia and behavioral despair. These altered behavioral responses were accompanied by reductions of striatal DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) restricted to the 6-OHDA group. Additionally, decreases on the hippocampal serotonin (5-HT) content were detected for the MPTP, 6-OHDA and rotenone groups. Notably, strong correlations were detected among the groups when 5-HT and DA were correlated with swimming (r=+0.97; P=0.001) and immobility (r=-0.90; P=0.012), respectively. Our data indicate that MPTP, 6-OHDA and rotenone, but not LPS were able to produce depressive-like behaviors accompanied primarily by hippocampal 5-HT reductions. Moreover, DA and 5-HT strongly correlated with "emotional" impairments suggesting an important participation of these neurotransmitters in anhedonia and behavioral despair after nigral lesions promoted by the neurotoxins.
Santiago
Ronise M
RM
Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brasil.
Barbieiro
Janaína
J
Lima
Marcelo M S
MM
Dombrowski
Patrícia A
PA
Andreatini
Roberto
R
Vital
Maria A B F
MA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000139:chemically induced* / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone; D012701:Serotonin / Q000378:metabolism*
D008070:Lipopolysaccharides; D012402:Rotenone; D012701:Serotonin; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine