The relationship between hindlimb disturbances, forelimb disturbances and catalepsy after increasing doses of muscimol injected into the striatal-pallidal complex

Vries, M. C. Vrijmoed-de; Tönissen, H.; Cools, Alexander R.

doi:10.1007/bf00215482

Cited by 18 publications

(7 citation statements)

References 21 publications

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“…Moreover, parkinsonian akinesia was associated with increased GABA levels in GP (Robertson et al 1991;Ochi et al 2000). Finally, to further confirm the view that sustained GABA inhibition within GP induced hypolocomotion, GABA receptor agonists injected in GP induced catalepsy (Pycock et al 1976;Vrijmoed-de Vries et al 1987) while GABA receptors antagonists reversed parkinsonian symptoms (Maneuf et al 1994). How high doses of NVP-AAM077 activate the indirect pathway remains matter of a conjecture.…”

Section: Discussionmentioning

confidence: 84%

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Differential effect of NR2A and NR2B subunit selective NMDA receptor antagonists on striato‐pallidal neurons: relationship to motor response in the 6‐hydroxydopamine model of parkinsonism

Fantin

Auberson

Morari

2008

Journal of Neurochemistry

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We previously demonstrated that NMDA receptors containing the NR2A or NR2B subunits differentially regulate striatal output pathways. We now investigate whether such a differential control is altered under parkinsonian conditions and whether subunit selective antagonists have different abilities to attenuate parkinsonian-like motor deficits. Three microdialysis probes were simultaneously implanted in the dopamine-depleted striatum, globus pallidus and substantia nigra reticulata of 6-hydroxydopamine hemilesioned rats. The NR2A antagonist NVP-AAM077 perfused in the striatum reduced pallidal GABA, but not glutamate, levels whereas the NR2B antagonist Ro 25-6981 was ineffective. Neither antagonist affected striatal or nigral amino acid levels. To investigate whether these neurochemical responses were predictive of different antiparkinsonian activities, antagonists were administered systemically and motor activity evaluated in different motor tasks. Neither antagonist attenuated akinesia/bradykinesia in the bar and drag test. However, NVP-AAM077 dually modulated rotarod performance (low doses being facilitatory and higher ones inhibitory) while Ro 25-6981 monotonically improved it. Microdialysis revealed that motor facilitating doses reduced pallidal GABA levels while motor inhibiting doses increased them. We conclude that, under parkinsonian conditions, the striato-pallidal pathway is driven by striatal NR2A subunits. Motor improvement induced by NVP-AAM077 and Ro 25-6981 is accomplished by blockade of striatal NR2A and extrastriatal NR2B subunits, respectively.

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Section: Discussionmentioning

confidence: 84%

“…Finally, to further confirm the view that sustained GABA inhibition within GP induced hypolocomotion, GABA receptor agonists injected in GP induced catalepsy (Pycock et al. 1976; Vrijmoed‐de Vries et al. 1987) while GABA receptors antagonists reversed parkinsonian symptoms (Maneuf et al.…”

Section: Discussionmentioning

confidence: 99%

Differential effect of NR2A and NR2B subunit selective NMDA receptor antagonists on striato‐pallidal neurons: relationship to motor response in the 6‐hydroxydopamine model of parkinsonism

Fantin

Auberson

Morari

2008

Journal of Neurochemistry

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“…With that in mind we have used the so-called paw test. This paw test was originally developed to study the influence of intrastriatal injections of GABAergic drugs on the ability of rats to withdraw their fore-and hindlimbs (Vrijmoed de Vries et al 1987). The present study with the paw test shows that it might be a good animal model for screening neuroleptic drugs for several reasons.…”

Section: Discussionmentioning

confidence: 84%

“…We therefore decided to test this hypothesis in a behavioural paradigm: the paw test. This test has been shown to be able to measure differentially the ability of a rat to retract its forelimbs and its hindlimbs (Vrijmoed de Vries et al 1987). The results show that the paw test might be a useful model for detecting atypical neuroleptic drugs.…”

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confidence: 80%

The paw test: a behavioural paradigm for differentiating between classical and atypical neuroleptic drugs

Ellenbroek

et al. 1987

Psychopharmacology

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An often used animal model based on the effects of neuroleptics on spontaneous behaviour is the catalepsy test. However, this test seems to be particularly insensitive to the atypical neuroleptics thioridazine and, especially, clozapine. We have therefore developed an alternative test, the paw test, which measures the ability of drugs to prevent the spontaneous withdrawal of fore- and hindlimbs in rats, and have compared this with the classical catalepsy test. The results show that: 1) the classical neuroleptic drugs haloperidol and chlorpromazine, the atypical neuroleptic drugs clozapine and thioridazine, the potential atypical neuroleptic drugs molindone and SCH 23390, and the potential classical neuroleptic drug metoclopramide are potent in increasing the hindlimb retraction time; 2) the paw test discriminates between classical neuroleptics which are equipotent in prolonging both the forelimb (FRT) and hindlimb retraction time (HRT) an atypical neuroleptics which are much more potent in prolonging HRT than in prolonging FRT; 3) the non-neuroleptic drugs desipramine, diazepam and morphine do not influence the variables measured in the paw test, although morphine does produce catalepsy; 4) Molindone as well as SCH 23390 behave like atypical neuroleptic drugs in the paw test. In comparison with the classical wood block catalepsy test, the paw test is shown to be superior for predicting the profile of the neuroleptics tested. Although more neuroleptics and non-neuroleptics have to be tested to determine whether false positives and false negatives do occur, we feel that the paw test might be an interesting animal model, because the increase in hindlimb retraction time was associated with the antipsychotic potential, whereas the increase in forelimb retraction time was associated with the potential to induce so-called extrapyramidal side effects.

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“…Among the experiments with 1 trial/day, the effects of prenatal phenytoin were shown on CWM errors for both path-A and path-B, but the effects were (as before) much larger for path-B (Vorhees and Minck, 1989). After prenatal valproic acid exposure, offspring showed a significant increase in CWM errors only when errors on path-A and path-B were combined (Vorhees, 1987c). The latter experiment was replicated and expanded to test the prenatal effects of valproic acid versus trans-2-ene-valproic acid, a potential therapeutic analogue that is not teratogenic as is valproic acid.…”

Section: Assessing Navigation In Rodentsmentioning

confidence: 99%

Cincinnati water maze: A review of the development, methods, and evidence as a test of egocentric learning and memory

Vorhees¹,

Williams²

2016

Neurotoxicology and Teratology

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Advantageous maneuvering through the environment to find food and avoid or escape danger is central to survival of most animal species. The ability to do so depends on learning and remembering different locations, especially home-base. This capacity is encoded in the brain by two systems: one using cues outside the organism (distal cues), allocentric navigation, and one using self-movement, internal cues (proximal cues), for egocentric navigation. Whereas allocentric navigation involves the hippocampus, entorhinal cortex, and surrounding structures, egocentric navigation involves the dorsal striatum and connected structures; in humans this system encodes routes and integrated paths and when over-learned, becomes procedural memory. Allocentric assessment methods have been extensively reviewed elsewhere. The purpose of this paper is to review one specific method for assessing egocentric, route-based navigation in rats: the Cincinnati Water Maze (CWM). The test is an asymmetric multiple-T maze arranged in such a way that rats must learn to find path openings along walls rather at ends in order to reach the goal. Failing to do this leads to cul-de-sacs and repeated errors. The task may be learned in the light or dark, but in the dark, wherein distal cues are eliminated, provides the best assessment of egocentric navigation. When used in conjunction with tests of other types of learning, such as allocentric navigation, the CWM provides a balanced approach to assessing the two major forms of navigational learning and memory found in mammals.

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The relationship between hindlimb disturbances, forelimb disturbances and catalepsy after increasing doses of muscimol injected into the striatal-pallidal complex

Cited by 18 publications

References 21 publications

Differential effect of NR2A and NR2B subunit selective NMDA receptor antagonists on striato‐pallidal neurons: relationship to motor response in the 6‐hydroxydopamine model of parkinsonism

Differential effect of NR2A and NR2B subunit selective NMDA receptor antagonists on striato‐pallidal neurons: relationship to motor response in the 6‐hydroxydopamine model of parkinsonism

The paw test: a behavioural paradigm for differentiating between classical and atypical neuroleptic drugs

Cincinnati water maze: A review of the development, methods, and evidence as a test of egocentric learning and memory

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