6-Hydroxydopamine lesion of the rat prefrontal cortex impairs motor initiation but not motor execution

Hauber, Wolfgang; Bubser, Michael; Schmidt, Werner

doi:10.1007/bf00228988

Cited by 31 publications

(12 citation statements)

References 39 publications

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“…Specifically, depletion of prefrontal cortex DA has been shown to cause deficits in movement initiation in a simple reaction time task (Hauber et al 1994) and a role for the frontal cortex has been proposed for deficits in reaction time observed in Parkinson's disease, as well (Berry et al 1999). In the present study, the animals with the largest striatal lesion sustained a 55% decrease in prefrontal DA, thus contribution of this structure to the impairments in this group of animals cannot be ruled out.…”

Section: Discussionmentioning

confidence: 55%

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Smith

Amalric²,

Koob

et al. 2002

Neuropsychopharmacology

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Overt symptoms of Parkinson's disease do not manifest themselves until there is a substantial loss of the dopaminergic nigrostriatal projection. However, as neuroprotective strategies are developed, it will be essential to detect the disease in its preclinical phase. Performance on conditioned reaction time tasks is known to be impaired by extensive 6-hydroxydopamine-induced lesions of theThe primary neuropathology of Parkinson's disease is the loss of dopamine (DA) neurons within the substantia nigra (SN) and massive depletion of DA in the striatum, the terminal region of the SN. This loss of DA appears to be responsible for the most prominent symptoms of Parkinson's disease. The degree of neurological deficit is related to the loss of striatal DA (Hornykiewicz and Kish 1987). The neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), used extensively to induce selective loss of DA neurons within the SN, provide animal models that share several of the characteristics of Parkinson's disease (see reviews by Zigmond and Keefe 1997;Jenner and Marsden 1986;Gerlach and Riederer NO . 6 Bilateral 6-OHDA on Reaction Time 7571996; Przedborski and Jackson-Lewis 1998). In addition, whereas intrastriatal injection of indirect DA agonists induces stereotypy (Costall et al. 1973;Statton and Solomon 1984), 6-OHDA lesions of the striatum block this stereotyped behavior (Price and Fibiger 1974). Finally, chronic administration of DA receptor antagonists produce extrapyramidal effects reminiscent of Parkinson's disease, and this is believed to be due to their action at D 2 receptors located in the striatum (Coffin et al. 1989). Although resting tremor and muscular rigidity are generally not reported in rodents after pharmacological manipulation of the nigrostriatal pathway, deficits in movement initiation and execution have been studied using several tests including a conditioned reaction time task. In this task, animals are typically required to respond in a particular way and within a limited period in order to receive a reward, such as a food pellet. This behavioral paradigm is responsive to pharmacological manipulation of dopaminergic neurotransmission mediated by the D 2 subtype of DA receptors Koob 1987, 1989;Amalric et al. 1993Amalric et al. , 1995Smith et al. 2000). For example, we have shown that low dose blockade of D 2 receptors, but not D 1 or D 3 receptors, decreased correct responses in the conditioned reaction time task, increased delayed responses, and lengthened reaction time in a manner suggestive of dysfunctions in movement initiation (Amalric et al. 1993;Smith et al. 2000). Moreover, deficits in reaction time have also been reported in Parkinson's disease (Evarts et al. 1981;Gauntlett-Gilbert and Brown 1998;Berry et al. 1999). These deficits appear to be mediated by the nigrostriatal dopaminergic pathway, as 6-OHDA-induced loss of SN neurons and striatal DA, and not accumbal DA, produces impairments in this task (Amalric and Koob 1987), and intrastriatal infusion...

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Section: Discussionmentioning

confidence: 55%

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Smith

Amalric²,

Koob

et al. 2002

Neuropsychopharmacology

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“…Together, these findings provide support to our observation that rats subjected to a 6-OHDA infusion had an almost complete unilateral pDMS DA depletion. One caveat to note, however, is that we did not quantify the exact extent of the DA depletion, for example, by measuring striatal tissue levels of DA (Hauber et al, 1994). Thus, we cannot exclude that the extent of DA depletion induced in our present study differed from those quantified in previous studies using lower concentrations of 6-OHDA (Baunez and Robbins, 1999;Blandini et al, 2007;Brown and Robbins, 1991;Winkler et al, 2002).…”

Section: Histologymentioning

confidence: 55%

Disconnection of the Entorhinal Cortex and Dorsomedial Striatum Impairs the Sensitivity to Instrumental Contingency Degradation

Lex

Hauber

2010

Neuropsychopharmacol

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The capacity to detect changes in the causal efficacy of actions is mediated by a number of brain areas, including the entorhinal cortex (EC) and the posterior part of the dorsomedial striatum (pDMS). In this study we examined whether interactions between the EC and pDMS are required to detect changes in the instrumental contingency. Rats that received EC-pDMS disconnection lesions, that is, unilateral cell body lesions of the EC and contralateral dopamine depletions of the pDMS, were trained to press two levers, with one delivering food pellets and the other a sucrose solution. Thereafter, we tested whether rats were sensitive (1) to a selective devaluation of the value of one of two outcomes using a specific satiety procedure, and (2) to a selective degradation of one of two contingencies controlling instrumental choice behavior. Our results reveal that rats with EC-pDMS disconnection lesions were sensitive to outcome devaluation. However, unlike rats with sham lesions or unilateral EC and pDMS lesions, rats with EC-pDMS disconnection lesions showed a reduced sensitivity to contingency degradation. These findings suggest that EC and pDMS may be part of a neural system that supports the detection of changes in the causal relationship between an action and its consequences.

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“…In addition to mnemonic and attentional functions, the rat FC is also involved in the contl-ol/pI-eparation of motor functions [5,9,25]. Moreover, it has been suggested that the shoulder region of the FC may be regarded as the pre-motor cortex in the rat [36].…”

Section: Discussionmentioning

confidence: 99%

Intact spatial discrimination performance but impaired reaction time performance after frontal cortex lesions in the rat

Blokland

Broersen

Uylings

et al. 2003

Neuroscience Res Communica

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SUMMARYIn the present study the consequences of frontal cortex (FC) lesions on spatial discl-iminatiol7 learning and reaction time performance were assessed in rats. Spatial working-and reference memory were tested simultaneously in a cone field task. It was found that FC lesions did not impair both aspects of spatial discrimination performance in this task. In a choice reaction time task the FC lesion decreased the response speed (reaction time and motor time). Detailed analysis of the reaction times indicated that these effects could be attributed to an impaired motor preparation and/or an attention deficit. The present study suggests that claims of deficit in learning and memory following FC lesions should take into account possible effects of motor pl-epal-ation/execLrtioll and attention.KEY WORDS: frontal cortex, spatial, reaction time, working memory, reference memory, attentionIn an extensive review on the role of the frontal cortex (FC) Kolb indicated that the main function of this part of the FC could be related with the temporal organization of behavior in rats [3Oj. Similar to humans and non-human primates, sub-regions of the frontal cortex of the rat can be dissociated on basis of anatomy and cognitive functions [ 1,18,26,28,30,3 1,42,45], but see [ 11,401. With respect to lesions of the medial FC, which may be regarded as the rat homologue of the dorsolatcral prefrontal cortex of primates [24,31], there appears to be a discrepancy between the data

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6-Hydroxydopamine lesion of the rat prefrontal cortex impairs motor initiation but not motor execution

Cited by 31 publications

References 39 publications

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Disconnection of the Entorhinal Cortex and Dorsomedial Striatum Impairs the Sensitivity to Instrumental Contingency Degradation

Intact spatial discrimination performance but impaired reaction time performance after frontal cortex lesions in the rat

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