The Placement of a Striatal Ibotenic Acid Lesion Affects Skilled Forelimb Use and the Direction of Drug-Induced Rotation

doi:10.1016/S0361-9230(96)00083-4

Brain Research Bulletin

Volume 41, Issue 6, 1996, Pages 409-416

https://doi.org/10.1016/S0361-9230(96)00083-4 Get rights and content

Abstract

The motor consequences of excitotoxic striatal damage have been evaluated extensively in the rat, using tests of whole body motor asymmetry and of deficits in skilled paw and limb movements. However conflicting results of both the type and extent of behavioural deficits have been reported, particularly in the direction of rotation observed in response to the dopamine receptor agonist, apomorphine. The present study investigated the effect of unilateral ibotenic acid lesions in the dorsal striatum of the adult rat, placed at either anterior, posterior, medial, or lateral loci, on rotation in response to both amphetamine and apomorphine, and in the “staircase test” of skilled forelimb use. In a 2 × 2 matrix design experiment, adult female albino rats received a double unilateral lesion of 0.5 μl 0.06 M ibotenic acid injected at each of two sites either anterior (medial and lateral), posterior (medial and lateral), medial (anterior and posterior), or lateral (anterior and posterior). Rats that received posterior lesions showed a marked ipsilateral rotation in response to both amphetamine and apomorphine, while animals receiving anterior lesions showed little ipsilateral or a slight contralateral bias. Rats receiving lateral lesions showed a marked impairment of contralateral paw use on the “staircase test,” while animals with medial lesions showed no significant difference to control unoperated animals. These results confirm the somatotopic organisation of the dorsal striatum in its control of motor functions, and indicate the need to take into account the locus of an excitotoxic lesion in the design of lesion and transplantation studies if we are to achieve reliable tests of the behavioural deficits and recovery. Copyright © 1996 Elsevier Science Inc.

Section snippets

INTRODUCTION

Excitotoxic lesions of the rat neostriatum produce anatomical and biochemical changes, and associated behavioural deficits, that mimic those of Huntington's disease 40, 41, 44. Now that the gene for Huntington's disease has been identified [20]and novel strategies for treatment are being actively considered [34], there is a renewed interest in understanding the functional organisation of the rat striatum to provide better animal models of the human disease. For example, striatal lesions

Animals

The experiment used 46 young adult female rats of the CFY strain (Interfauna, Huntingdon), aged 12 weeks at the start of the experiment. All animals were housed in groups of four animals per cage under a natural light-dark cycle. Food and water was available ad lib, other than during the staircase test training, during which the rats were maintained on a food deprivation regime of 12 g per animal per day, given immediately after the daily test session. The rats were randomly allocated into five

Rotation

The mean scores of rotation in response to d-amphetamine are shown in Fig. 1. The rats that had received anterior lesions showed a net contralateral rotation while all other groups showed net ipsilateral rotation. Analysis of variance indicated that the mean scores between groups approached but just failed to reach significance, F(3,32) = 2.81, p = 0.055). Post hoc comparisons indicated that only the posterior group showed a significant ipsilateral rotational asymmetry [Sidak's t(4, 32) = 3.81,

DISCUSSION

The present study showed that the site of an ibotenic acid lesion within the dorsal striatum affects the nature of the deficit in both circling behaviour and skilled forelimb use. Posterior lesions induce marked ipsilateral rotation in response to both d-amphetamine and apomorphine, while anterior lesions induce no such rotational bias. Lateral lesions cause marked impairment of paw reaching in the “staircase” test while medial lesions have no significant effect on this measure.

Acknowledgements

This research was supported by the Hereditary Disease Foundation, the Wellcome Trust, and the Medical Research Council.

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¹: Current address: Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden.

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The Placement of a Striatal Ibotenic Acid Lesion Affects Skilled Forelimb Use and the Direction of Drug-Induced Rotation

Abstract

Section snippets

INTRODUCTION

Animals

Rotation

DISCUSSION

Acknowledgements

Neuroscience

Brain Res.

Neuroscience

Behav. Brain Res.

Brain Res.

Neuropharmacology

Neurosci. Res.

Neurosci. Lett.

Neurosci. Lett.

Brain. Res.

Neuroscience

Brain Res.

J. Neurosci. Methods

Prog. Brain Res.

Brain Res. Bull.

Neuropharmacology

Brain Res.

Neuroscience

Neuroscience

Behav. Brain Res.

Behav. Brain Res.

Exp. Neurol.

Brain Res.