Lesions of dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area enhance depressive-like behavior in rats.
Depression is the most common psychiatric complication in Parkinson's disease (PD). The pathophysiological events leading to PD-associated depression, however, remain largely unknown. The present study tested the differential implication of dopaminergic systems in depressive-like behavior in rats and its response to l-Dopa and the selective serotonin reuptake inhibitor citalopram. The learned helplessness model was used as a behavioral paradigm. Rats were lesioned in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) and assigned to subgroups with respect to the stereologically verified extent of the nigral and/or VTA degeneration. Both lesions increased depressive-like behavior in rats, which was reduced by both citalopram and l-Dopa treatment. We conclude that dopaminergic lesions of either the SNc or the VTA contribute to the manifestation of depressive-like behavior in rats. The effects of citalopram administration on depressive behavior induced by lesions of dopaminergic brain regions furthermore suggest an involvement of serotonergic pathways in dopaminergic cell loss-induced depression.
Winter
Christine
C
Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Germany. christine.winter@charite.de
von Rumohr
Anke
A
Mundt
Adrian
A
Petrus
Dominique
D
Klein
Julia
J
Lee
Thomas
T
Morgenstern
Rudolf
R
Kupsch
Andreas
A
Juckel
Georg
G
D018663:Adrenergic Agents / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015283:Citalopram / Q000008:administration & dosage; D003863:Depression / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D007839:Functional Laterality; D006380:Helplessness, Learned; D007980:Levodopa / Q000008:administration & dosage; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D045442:Rotarod Performance Test / Q000379:methods; D013378:Substantia Nigra / Q000166:cytology* / Q000293:injuries / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000166:cytology* / Q000293:injuries / Q000502:physiology
D018663:Adrenergic Agents; D000928:Antidepressive Agents; D015283:Citalopram; D007980:Levodopa; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase