Lesions of dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area enhance depressive-like behavior in rats

Behav Brain Res. 2007 Dec 3;184(2):133-41. doi: 10.1016/j.bbr.2007.07.002. Epub 2007 Jul 7.


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.

MeSH terms

  • Adrenergic Agents / pharmacology
  • Amphetamine / pharmacology
  • Analysis of Variance
  • Animals
  • Antidepressive Agents / administration & dosage
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Citalopram / administration & dosage
  • Depression / drug therapy
  • Depression / etiology
  • Depression / pathology
  • Depression / physiopathology*
  • Disease Models, Animal
  • Functional Laterality
  • Helplessness, Learned
  • Levodopa / administration & dosage
  • Male
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Neurons / physiology*
  • Oxidopamine / adverse effects
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Rotarod Performance Test / methods
  • Substantia Nigra / cytology*
  • Substantia Nigra / injuries
  • Substantia Nigra / physiology
  • Tyrosine 3-Monooxygenase / metabolism*
  • Ventral Tegmental Area / cytology*
  • Ventral Tegmental Area / injuries
  • Ventral Tegmental Area / physiology


  • Adrenergic Agents
  • Antidepressive Agents
  • Citalopram
  • Levodopa
  • Oxidopamine
  • Amphetamine
  • Tyrosine 3-Monooxygenase