Elsevier

Neuroscience

Volume 153, Issue 4, 2 June 2008, Pages 1213-1224
Neuroscience

Neuroanatomy
Differential behavioral effects of partial bilateral lesions of ventral tegmental area or substantia nigra pars compacta in rats

https://doi.org/10.1016/j.neuroscience.2008.01.084Get rights and content

Abstract

Akinesia (or absence of movement) is a prominent feature of Parkinson's disease. Akinetic symptoms, however, are also observed in depression and schizophrenia, which support the hypothesis that akinesia involves more than only motor behavior. A common feature of these disorders is the disruption of dopamine homeostasis in the CNS. Here we aimed at relating the respective involvement of the nigrostriatal and mesocortical dopaminergic pathways to akinesia. We investigated in the rat the relative effects of selective bilateral partial lesions of substantia nigra pars compacta (SNc) or ventral tegmental area (VTA) which did not affect locomotion, on fine motor, motivational and cognitive behaviors. Motor impairments were measured by the evaluation of fine motor control in the stepping test and in the paw reaching test. Cognitive functions were assessed by various paradigms: spontaneous alternation in the Y maze and object exploration task. Motivational behavior was evaluated by the 100-pellets test. The results suggested that specific behavioral impairments are obtained following selective lesions of either SNc or VTA. SNc-lesioned rats exhibited deficits in fine motor functions as previously described in animal models of Parkinson's disease, whereas VTA-lesioned rats demonstrated traits of perseveration without significant motor impairments.

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Animals

Twenty-nine Wistar rats (Depré, St. Doulchard, France) weighing 450–480 g were housed under controlled conditions of light (12-h light/dark cycle, i.e. lights on from 07:00–19:00 h), temperature (22 °C) and humidity. Food and water were available ad libitum. All experiments were carried out in accordance with the European Committee Council Directive of 24 November 1986 (86/609/EEC) and were approved by the local ethical committee. All reasonable efforts were made to minimize animal suffering

Extent of lesion

Given the aim of the present study, it was imperative that our lesions be large enough to cover the target area, but strictly restricted to either the SNc or the VTA. We have previously shown with the same model that (i) bilateral lesions were highly comparable on both hemispheres and that (ii) partial lesions of the SNc and VTA were restricted to the targeted nucleus (Pioli et al., 2004). The extent of 6-OHDA-induced lesion in SNc and VTA was quantified by unbiased stereological counting of

Discussion

The present study shows that distinctive patterns of behavioral impairment are obtained following selective lesion of either the SNc or VTA. Our results imply that the SNc might be primarily involved in motor-related akinesia behavior, while the VTA is preferentially associated with a perseverative behavior.

Acknowledgments

We wish to thank L. Cardoit and S. Dovero for the technical assistance. E.Y.P. was supported by a fellowship from the Ministère de la Recherche et de la Technologie (MRT) and W.M. was a Marie Curie Fellow of the European Community (HPMF-2001-01300). The University Victor Segalen, the CNRS and the IFR (INSERM No. 8; CNRS No. 13) funded this study.

References (86)

  • R. Lalonde

    The neurobiological basis of spontaneous alternation

    Neurosci Biobehav Rev

    (2002)
  • C.S. Lee et al.

    Dopaminergic neuronal degeneration and motor impairments following axon terminal lesion by instrastriatal 6-hydroxydopamine in the rat

    Neuroscience

    (1996)
  • E.A. Loh et al.

    Evaluation of response perseveration of rats in the radial arm maze following reinforcing and nonreinforcing drugs

    Pharmacol Biochem Behav

    (1993)
  • S.E. Loughlin et al.

    Substantia nigra and ventral tegmental area projections to cortex: topography and collateralization

    Neuroscience

    (1984)
  • L. Mallet et al.

    Compulsions, Parkinson's disease, and stimulation

    Lancet

    (2002)
  • H. Mollion et al.

    Dissociable effects of dopaminergic therapy on spatial versus non-spatial working memory in Parkinson's disease

    Neuropsychologia

    (2003)
  • C.P. Montoya et al.

    The “staircase test”: a measure of independent forelimb reaching and grasping abilities in rats

    J Neurosci Methods

    (1991)
  • A. Nieoullon

    Dopamine and the regulation of cognition and attention

    Prog Neurobiol

    (2002)
  • T. Ogura et al.

    Impaired acquisition of skilled behavior in rotarod task by moderate depletion of striatal dopamine in a pre-symptomatic stage model of Parkinson's disease

    Neurosci Res

    (2005)
  • A.M. Owen et al.

    Spatial and non-spatial working memory at different stages of Parkinson's disease

    Neuropsychologia

    (1997)
  • E. Pioli et al.

    Partial bilateral mesencephalic lesions affect D1 but not D2 binding in both the striatum and cortex

    Neurochem Int

    (2004)
  • K.E. Sabol et al.

    Dopamine depletion in a striatal subregion disrupts performance of a skilled motor task in the rat

    Brain Res

    (1985)
  • K. Sakai et al.

    Effect of bilateral 6-OHDA lesions of the substantia nigra on locomotor activity in the rat

    Brain Res

    (1994)
  • D.P. Salmon et al.

    Neurobiology of skill and habit learning

    Curr Opin Neurobiol

    (1995)
  • J.S. Schneider et al.

    Chronic exposure to low doses of MPTPI. Cognitive deficits in motor asymptomatic monkeys

    Brain Res

    (1990)
  • R.K. Schwarting et al.

    The unilateral 6-hydroxydopamine lesion model in behavioral brain researchAnalysis of functional deficits, recovery and treatments

    Prog Neurobiol

    (1996)
  • R.K. Schwarting et al.

    Unilateral 6-hydroxydopamine lesions of meso-striatal dopamine neurons and their physiological sequelae

    Prog Neurobiol

    (1996)
  • T. Shimura et al.

    Ventral tegmental lesions reduce overconsumption of normally preferred taste fluid in rats

    Behav Brain Res

    (2002)
  • L.W. Swanson

    The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat

    Brain Res Bull

    (1982)
  • K. Taghzouti et al.

    Disturbances in exploratory behavior and functional recovery in the Y and radial mazes following dopamine depletion of the lateral septum

    Behav Neural Biol

    (1986)
  • H. Theoret et al.

    Stereological evaluation of substantia nigra cell number in normal and hemispherectomized monkeys

    Brain Res

    (1999)
  • A.M. Thierry et al.

    Electrophysiological evidence for non-dopaminergic mesocortical and mesolimbic neurons in the rat

    Brain Res

    (1980)
  • M.J. West

    Stereological methods for estimating the total number of neurons and synapses: issues of precision and bias

    Trends Neurosci

    (1999)
  • I.Q. Whishaw et al.

    The structure of skilled forelimb reaching in the rat: a proximally driven movement with a single distal rotatory component

    Behav Brain Res

    (1990)
  • N.M. White

    Mnemonic functions of the basal ganglia

    Curr Opin Neurobiol

    (1997)
  • E. Yadin et al.

    Spontaneous alternation behavior: an animal model for obsessive-compulsive disorder?

    Pharmacol Biochem Behav

    (1991)
  • P. Barneoud et al.

    Evaluation of simple and complex sensorimotor behaviours in rats with a partial lesion of the dopaminergic nigrostriatal system

    Eur J Neurosci

    (2000)
  • C. Baunez et al.

    Enhanced food-related motivation after bilateral lesions of the subthalamic nucleus

    J Neurosci

    (2002)
  • E. Bezard et al.

    Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive MPTP-lesioned macaque model of Parkinson's disease

    J Neurosci

    (2001)
  • R.G. Brown et al.

    Cognitive-motor dysfunction in Parkinson's disease

    Eur Neurol

    (1996)
  • M.C. Buhot et al.

    Changes in exploratory activity following stimulation of hippocampal 5-HT1A and 5-HT1B receptors in the rat

    Hippocampus

    (1995)
  • D.B. Carr et al.

    Dopamine terminals synapse on callosal projection neurons in the rat prefrontal cortex

    J Comp Neurol

    (2000)
  • D.B. Carr et al.

    GABA-containing neurons in the rat ventral tegmental area project to the prefrontal cortex

    Synapse

    (2000)
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