Reactive capacity: A sensitive behavioral marker of movement initiation and nigrostriatal dopamine function

Spirduso, Waneen W.; Gilliam, P. E.; Schallert, Timothy; Upchurch, Meg; Vaughn, Dana M.; Wilcox, Richard E.

doi:10.1016/0006-8993(85)90274-4

Cited by 121 publications

(24 citation statements)

References 25 publications

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“…Based on our previous studies, we suggest that at least a portion of this action is mediated by an action of the agonist on striatal dopamine receptors (Woff et al 1980;Spirduso et al 1984Spirduso et al , 1985. A tentative framework for the present results is suggested by the differential actions of dopamine itself in relation to D1 and D2 receptor mediated responses (Matthews and German 1986).…”

Section: Discussionsupporting

confidence: 66%

Apomorphine doses impair the reaction time of fast reacting but not slow reacting rats

Wilcox

Spirduso

1988

Psychopharmacology

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Previously, several studies in our laboratories have linked the ability to initiate movement rapidly (reactive capacity) in several rat strains to markers of nigrostriatal dopamine function. In the present investigation we wished to determine the extent to which fast-reacting (FR) and slow-reacting (SR) rats responded differentially to the effects of dopamine agonist (apomorphine) administration. Fisher 344 rats were operantly conditioned on a shock-avoidance, reactive capacity task which requires extremely fast, ballistic, lever release responses. In FR, but not in SR rats, significant dose-dependent decreases in the per cent of successful avoidance trials were observed in response to apomorphine doses. Moreover, apomorphine brought responding in the FR animals to levels below that of the SR rats. Performance of the SR rats was unaffected by drug treatments. A number of interpretations are consistent with these preliminary data, including the idea that basal differences in speed of reaction and differential responses to a dopamine agonist, antiparkinsonian agent may both be associated with a similar mechanism: differential activation of compartmentalized striatal efferent systems.

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Section: Discussionsupporting

confidence: 66%

Apomorphine doses impair the reaction time of fast reacting but not slow reacting rats

Wilcox

Spirduso

1988

Psychopharmacology

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“…After dopamine depletion, simulated SNr output was insufficiently reduced to signal selection, implying a difficulty in initiating movement. A series of studies have shown an increased difficulty of movement initiation after a unilateral 6-OHDA lesion in rat (Spirduso et al, 1985;Olsson et al, 1995;Kirik et al, 1998;Phillips and Brown, 1999), consistent with the akinesia typical of Parkinson's disease.…”

Section: Putative Action Selection Functions Of the Bgmentioning

confidence: 88%

A Physiologically Plausible Model of Action Selection and Oscillatory Activity in the Basal Ganglia

Humphries

Stewart²,

Gurney³

2006

J. Neurosci.

341

439

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The basal ganglia (BG) have long been implicated in both motor function and dysfunction. It has been proposed that the BG form a centralized action selection circuit, resolving conflict between multiple neural systems competing for access to the final common motor pathway. We present a new spiking neuron model of the BG circuitry to test this proposal, incorporating all major features and many physiologically plausible details. We include the following: effects of dopamine in the subthalamic nucleus (STN) and globus pallidus (GP), transmission delays between neurons, and specific distributions of synaptic inputs over dendrites. All main parameters were derived from experimental studies. We find that the BG circuitry supports motor program selection and switching, which deteriorates under dopamine-depleted and dopamine-excessive conditions in a manner consistent with some pathologies associated with those dopamine states. We also validated the model against data describing oscillatory properties of BG. We find that the same model displayed detailed features of both ␥-band

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“…Animal lesion studies have demonstrated that SRT performance in rats is highly sensitive to small (10-25%) dopamine depletions in striatum when the animal is required to react with maximal speed [40]. In humans, healthy aging is associated with striatal DAT reductions that are at least 50%, as shown by both in vitro homogenate binding studies [2,10,53] and in vivo radioligand studies [43,44,46,47], and these reductions are commensurate with agerelated reductions in the number of dopaminergic cell bodies in the pars compacta of the substantia nigra (SNc) [26].…”

Section: Relationship To Other Preclinical and Clinical Studiesmentioning

confidence: 99%

“…Whereas, early animal studies held that a depletion of nigrostriatal dopamine in the order of 85-95% was necessary to produce chronic impairment in most motor tests [33,37], more specialized tasks were subsequently shown to have sensitivity to much smaller lesions [8,40]. Simple Reaction Time (the time interval from the presentation of a stimulus until a response is initiated; SRT) performance in rats has been observed to be highly sensitive to small (10-25%) dopamine depletions in striatum when the animal is required to react with maximal speed [40]. Moreover, interresponse time on a self-directed lever-pressing task [36] has been shown to be sensitive to small depletions (mean=29%) in ventrolateral striatum [8].…”

Section: Introductionmentioning

confidence: 99%

Striatal dopamine transporters correlate with simple reaction time in elderly subjects

Dyck

Avery

MacAvoy

et al. 2008

Neurobiology of Aging

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The decline in motor performance that accompanies advanced age has unclear neurobiological substrates but may relate, in part, to degeneration of the nigrostriatal dopamine system. This research tested the hypothesis that striatal dopamine transporter (DAT) availability in healthy elderly individuals was related to measures of motor performance. Thirty-six healthy volunteers (18 male, 18 female) who ranged in age from 68 to 88 (75.4±4.9 years) received a neuropsychological evaluation that included two primary motor measures (tested with dominant hand): 1) Simple Reaction Time (SRT); and 2) Finger Tapping (FT). Subjects underwent SPECT scanning with [ 123 I]2ß-carbomethoxy-3ß-(4-iodophenyl)tropane ([ 123 I]ß-CIT) for measurement of striatal DAT availability. A ratio of specific to nondisplaceable brain uptake (i.e., V 3 ″=[striatal −occipital]/occipital), a measure proportional to the binding potential (B max /K D ), was derived. SRT was significantly correlated with striatal DAT availability with or without controlling for the contribution of age. However, contrary to hypothesis, FT was not correlated with striatal DAT availability. Comparison measures, including episodic memory and general intelligence, were also unrelated to striatal DAT availability. These results demonstrate that a loss of nigrostriatal dopaminergic function likely contributes to slowing of reaction speed with advancing age.

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Reactive capacity: A sensitive behavioral marker of movement initiation and nigrostriatal dopamine function

Cited by 121 publications

References 25 publications

Apomorphine doses impair the reaction time of fast reacting but not slow reacting rats

Apomorphine doses impair the reaction time of fast reacting but not slow reacting rats

A Physiologically Plausible Model of Action Selection and Oscillatory Activity in the Basal Ganglia

Striatal dopamine transporters correlate with simple reaction time in elderly subjects

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