Elsevier

Behavioural Brain Research

Volume 234, Issue 2, 1 October 2012, Pages 343-348
Behavioural Brain Research

Research report
Tongue force and tongue motility are differently affected by unilateral vs bilateral nigrostriatal dopamine depletion in rats

https://doi.org/10.1016/j.bbr.2012.07.003Get rights and content

Abstract

In addition to its cardinal symptoms of bradykinesia, muscle rigidity, resting tremor and postural disturbances, Parkinson's disease (PD) also affects orolingual motor function. Orolingual motor deficits can contribute to dysphagia, which increases morbidity and mortality in this population. Previous preclinical studies describing orolingual motor deficits in animal models of PD have focused on unilateral nigrostriatal dopamine (DA) depletion. In this study we compared the effects of unilateral vs bilateral 6-hydroxydopamine (6-OHDA)-induced DA depletion in rats trained to lick water from an isometric force-sensing disc. Rats received either unilateral or bilateral 6-OHDA into the medial forebrain bundle and were tested for four weeks post-lesion. Dependent variables included task engagement (the number of licks per session), tongue force (mean and maximum), and tongue motility (the number of licks per second). While both lesion groups exhibited decreased tongue force output, tongue motility deficits were present in only the group that received unilateral nigrostriatal DA depletion. Task engagement was not significantly diminished by 6-OHDA. Analysis of striatal DA tissue content revealed that DA depletion was ∼97% in the unilateral group and ∼90% in the bilateral group. These results suggest that while nigrostriatal DA depletion affects tongue force output, deficits in tongue motility may instead result from a functional imbalance in neural pathways affecting this midline structure.

Highlights

► Unilateral and bilateral nigrostriatal dopamine depletion affect orolingual motor function in rats. ► Both unilateral and bilateral nigrostriatal dopamine depletion decrease tongue force during licking. ► Tongue motility is decreased following unilateral but not bilateral nigrostriatal dopamine depletion. ► These results reveal a dissociation between these two movement modalities in the 6-hydroxydopamine rat model of Parkinson's disease.

Introduction

Parkinson's disease (PD) is an age-related neurodegenerative disease with characteristic symptoms that include bradykinesia, muscle rigidity, resting tremor and postural disturbances. These symptoms result primarily from degeneration of dopamine (DA) neurons in the substantia nigra, and depletion of DA in the nigrostriatal pathway [2], [11]. Preclinical studies have taken advantage of this well-characterized lesion by targeting the nigrostriatal pathway with neurotoxic agents such as 6-hydroxydopamine (6-OHDA) and MPTP (reviewed in [8]). These models, which typically involve unilateral DA depletion, generally recapitulate the cardinal symptoms of PD.

In addition to its cardinal symptoms, PD can also impair orolingual and pharyngeal motor function [1], [18], [27], [40]. These impairments can increase morbidity and mortality [25], primarily by disrupting the oral phase of swallowing [44]. In contrast to limb deficits (and with the exception of levodopa-induced oral dyskinesias [15]), preclinical attention to the primary effects of nigrostriatal DA depletion on orolingual motor function is a relatively recent development [13], [36], [41], [47]. These studies have reported that unilateral nigrostriatal DA depletion impairs tongue motility and protrusion force. The effects of bilateral nigrostriatal DA depletion on orolingual motor function have not been reported. This is an important consideration, not only because the tongue is a midline structure, but because onset in PD is typically unilateral, progressing bilaterally in later stages [23].

The purpose of this study was to compare the effects of bilateral and unilateral nigrostriatal DA depletion models on orolingual motor function in rats. Rats’ tongue force and tongue motility were measured as they licked water from an isometric disc as described previously by our lab [43], [51] and others [36], [41]. Orolingual motor function was measured prior to and for four weeks after treatment with 6-OHDA. We hypothesized that rats with bilateral striatal DA depletion would exhibit greater deficits in tongue force and tongue motility than rats with unilateral lesions.

Section snippets

Animals

Male Sprague–Dawley rats were obtained from Harlan. Rats were 3-months-old at the time of testing, were housed individually and were maintained on a 12 h light/dark cycle. After acclimation to the facility, access to water was gradually restricted with food made available ad libitum. The water restriction schedule allowed for slow weight gain and provided rats with necessary motivation to perform the water licking task. Procedures adhered to the Guide for the Care and Use of Laboratory Animals

Orolingual motor function

Pre-lesion values for body weight and the orolingual motor variables are provided in Table 1. None of the groups differed significantly with regard to body weight, tongue force, tongue motility or number of licks during these baseline measurements. Nigrostriatal DA depletion significantly attenuated tongue force in both lesion groups (Fig. 1). Although the effect for peak force did not differ significantly, maximum lick force was significantly decreased, F = 5.236, p = 0.01 (Fig. 2A and B). This

Discussion

In this study we found that nigrostriatal DA depletion impairs orolingual motor function in rats. While this finding is consistent with previous work, we extended these findings to report that bilateral DA depletion does not merely worsen the impairments observed in unilaterally lesioned rats, but rather affects orolingual motor function in qualitatively different ways. Specifically, although both lesion groups exhibited decreased tongue force, tongue motility deficits were limited to the

Acknowledgements

This work was supported by NIH grants AG023549, AG026491, the Kansas Training Program in Neurological and Rehabilitation Sciences (T32 HD57850), a Lied Endowed Basic Science Research grant, and by the Kansas Intellectual and Developmental Disabilities Research Center (HD02528).

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