Both pre- and post-lesion experiential therapy is beneficial in 6-hydroxydopamine dopamine-depleted female rats

Neuroscience. 2009 Jan 23;158(2):373-86. doi: 10.1016/j.neuroscience.2008.10.054. Epub 2008 Nov 7.


Experiential therapies, such as enriched environment (EE), have been shown to influence the neurodegenerative processes that underlie Parkinson's disease. We have previously demonstrated that EE promotes functional improvement in dopamine-depleted rats. Here we compare the influence of exposure to EE prior to versus after dopamine depletion in the 6-hydroxydopamine rat model of Parkinson's disease. Two groups of female rats were placed in an EE while two groups were housed in a standard environment (SE) for 6 weeks prior to receiving a unilateral nigrostriatal bundle infusion of the neurotoxin 6-hydroxydopamine. After the lesion, one group remained in EE, while the second EE group (Pre-Lesion EE) was moved into SE conditions. In addition, a third group of rats was now moved into EE (Post-lesion EE). A fourth group remained in SE throughout the experimental period. Rats were tested in skilled reaching and skilled walking tasks and in non-skilled motor function up to 4 weeks after lesion. The observations demonstrated beneficial effects of both pre- and post-lesion exposure to EE on skilled movement performance by promoting compensatory limb use and partial protection or restoration of skilled movement. Exposure to pre-lesion EE in particular promoted structural plasticity as indicated by increased expression of the main cytoskeletal component microtubule associated protein-2 in the lesion dorsal striatum. Continuous EE showed absence of rotational bias suggesting attenuated dopamine loss. These data indicate that enriched lifestyle before the onset of motor symptoms and rehabilitation programs after diagnosis might be beneficial in patients with Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine
  • Corticosterone / blood
  • Disease Models, Animal
  • Dopamine / deficiency*
  • Environment*
  • Exploratory Behavior
  • Female
  • Functional Laterality
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Locomotion / physiology
  • Microtubule-Associated Proteins / metabolism
  • Motor Skills / drug effects
  • Motor Skills / physiology
  • Neurotoxicity Syndromes* / etiology
  • Neurotoxicity Syndromes* / metabolism
  • Neurotoxicity Syndromes* / therapy
  • Neurotoxins / toxicity*
  • Oxidopamine / toxicity*
  • Rats
  • Rats, Long-Evans
  • Tyrosine 3-Monooxygenase / metabolism


  • MAP2 protein, rat
  • Microtubule-Associated Proteins
  • Neurotoxins
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Apomorphine
  • Dopamine
  • Corticosterone