Depressive-like neurochemical and behavioral markers of Parkinson's disease after 6-OHDA administered unilaterally to the rat medial forebrain bundle

Pharmacol Rep. 2017 Oct;69(5):985-994. doi: 10.1016/j.pharep.2017.05.016. Epub 2017 Jun 3.


Background: Although Parkinson's disease (PD) is characterized by progressive neurodegeneration of multiple neurotransmitter systems, 6-hydroxydopamine (6-OHDA) as a model substance is mainly used to selectively damage the nigrostriatal dopaminergic neurons and induce parkinsonian-like motor disturbances in rats. We hypothesized that high doses of this neurotoxin affecting other monoaminergic systems may also evoke the depressive-like behavior.

Methods: The impact of 6-OHDA (8, 12, 16μg/4μl) administered unilaterally into the medial forebrain bundle on the sucrose solution intake (a measure of anhedonia) and on the tissue levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the striatum (STR), substantia nigra (SN), prefrontal cortex (PFC) and hippocampus (HIP) was examined in rats pretreated or non-pretreated with desipramine.

Results: The highest dose of 6-OHDA reduced the preference for 3% sucrose solution both in rats without and with desipramine pretreatment. All used doses of 6-OHDA dramatically decreased DA content in the studied brain structures on the ipsilateral side. NA levels were severely decreased in the ipsilateral STR, HIP and PFC of rats non-pretreated with desipramine and to a much lesser extent in those pretreated with desipramine. In the SN, moderate decreases in NA level were found both in rats pretreated and non-pretreated with desipramine. Higher doses of 6-OHDA reduced 5-HT content in the ipsilateral STR, HIP and PFC, but not in the SN, only in rats non-pretreated with desipramine.

Conclusions: Administration of the highest dose of 6-OHDA without desipramine pretreatment evoked neurochemical and behavioral changes resembling the advanced PD with coexisting depression.

Keywords: Asymmetric behavior; Depressive-like behavior; Monoamine levels; Sucrose solution intake; Unilateral 6-OHDA lesion.

MeSH terms

  • Animals
  • Behavior, Animal
  • Depressive Disorder / chemically induced*
  • Dopamine / metabolism
  • Male
  • Medial Forebrain Bundle / drug effects*
  • Norepinephrine / metabolism
  • Oxidopamine / toxicity*
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / pathology
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism


  • Serotonin
  • Oxidopamine
  • Dopamine
  • Norepinephrine