Interaction between glutamatergic and dopaminergic tone in the nucleus accumbens of mice: evidence for a dual glutamatergic function with respect to psychomotor control

Svensson, Anders; Carlsson, Maria; Carlsson, Arvid

doi:10.1007/bf01244735

Cited by 41 publications

(16 citation statements)

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“…A unilateral injection of the competitive NMDA antagonist AP-5 caused the animals to rotate. The rotation was predominantly ipsilateral in monoaminergically intact animals, whereas the rotation in monoamine-depleted mice was exclusively contralateral (Svensson et al, 1992a). This shift in the direction of rotation was apparently due to lack of dopamine receptor stimulation, because in monoamine-depleted animals treated with the mixed dopamine agonist apomorphine, AP-5 caused the animals to rotate predominantly ipsilaterally (Svensson et al, unpublished findings).…”

Section: Introductionmentioning

confidence: 89%

“…The D2 receptor agonist quinpirole reversed the contralateral rotation induced by AP-5 in monoamine-depleted animals into ipsilateral rotation. In contrast, in monoamine-depleted mice treated with the dopamine D1 receptor agonist SKF 38393, AP-5 still induced contralateral turning (Svensson et al, 1992a). These findings suggest that glutamate in the accumbens both can stimulate and inhibit motor functions, and that interactions with dopamine D2 receptors are crucial for the balance between glutamatergic stimulation and inhibition of behaviour.…”

Section: Introductionmentioning

confidence: 89%

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Crucial role of the accumbens nucleus in the neurotransmitter interactions regulating motor control in mice

Svensson

Carlsson

1995

J. Neural Transmission

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Previous work, based on systemic drug administration, has shown that neurotransmitter interactions between dopaminergic, adrenergic, glutamatergic and cholinergic systems are involved in locomotor control in mice. In an attempt to identify the target sites in the brain of these interactions, we have started a series of experiments, where the drugs are administered intracerebrally in mice. The locomotor threshold doses of the competitive NMDA antagonist AP-5 and the noncompetitive NMDA antagonist MK-801 were investigated by means of local application in the accumbens nucleus of monoamine-depleted and monoaminergically intact mice, respectively. The threshold dose of AP-5 was lower in depleted than in intact animals, whereas the threshold dose of MK-801 was lower in monoaminergically intact than monoamine-depleted mice. The locomotor effects of AP-5 and the AMPA-kainate receptor antagonist CNQX were registered in monamine-depleted mice after local application in the accumbens or entopeduncular nucleus (= medial pallidum). Both AP-5 and CNQX stimulated locomotor activity in the accumbens, but had no effects in the entopeduncular nucleus. We have previously shown synergistic interactions with regard to locomotor stimulation in monoamine-depleted mice, between an NMDA antagonist and an alpha 2-adrenoceptor agonist or a dopamine D1 agonist (all drugs given systemically). In the present study the alpha 2-adrenoceptor agonist alpha-methylnoradrenaline was applied intracerebrally in combination with a subthreshold dose of MK-801 given intraperitoneally: Locomotor stimulation was produced after alpha-methyl-noradrenaline injection into the accumbens nucleus, but not after injection into the dorsal striatum, prefrontal cortex or thalamus. Likewise, local application of the D1 agonist SKF 38393, in combination with a subthreshold dose of MK-801 given intraperitoneally, point to an important role of the accumbens nucleus in motor control. Previous experiments based on systemic drug administration have also shown a synergistic interaction between a muscarine antagonist and an alpha 2-adrenoceptor agonist in monoamine-depleted mice. Local application of the muscarine antagonist methscopolamine, in combination with the alpha 2-adrenoceptor agonist clonidine given intraperitoneally, showed that the striatum, in this case both the ventral and dorsal parts of the striatum, is an important target for the muscarine antagonist. Unilateral injection of AP-5 into the accumbens nucleus of mice induces rotational behaviour: Previous findings have shown that the rotation is ipsilateral in monoaminergically intact animals, whereas monoamine-depleted animals rotate contralaterally. In addition, these findings have shown that dopamine D2 receptor stimulation seems to determine whether AP-5 will induce ipsilateral or contralateral rotation. In the present study we report further evidence for a crucial role of the D2 receptor in this respect. Finally, the rotational effects of AP-5 injected into the dorsal striatum or hippocampus were investiga...

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 89%

Crucial role of the accumbens nucleus in the neurotransmitter interactions regulating motor control in mice

Svensson

Carlsson

1995

J. Neural Transmission

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“…In animals with intact monoaminergic systems, we have suggested that the balance between the two feedback circuits is shifted towards the positive feedback circuit, perhaps owing to the excitatory dopaminergic input to this circuit. Hence, in this case AP-5 will reduce the glutamatergic tone in the positive feedback circuit, rather than in the negative feedback circuit, and this should lead to a relatively higher activity in the positive feedback circuit on the untreated side, and accordingly ipsilateral rotation (Svensson, 1992b).…”

Section: Introductionmentioning

confidence: 98%

“…This shift in the direction of rotation was apparently due to lack of dopamine receptor stimulation, since AP-5 induced ipsilateral rotation in monoamine-depleted mice treated with the mixed dopamine agonist apomorphine (unpublished findings). These findings led us to suggest that glutamatergic neurotransmission in the nucleus accumbens has a dual function with regard to motor control (Svensson et al, 1992b).…”

Section: Introductionmentioning

confidence: 98%

The muscarine antagonist methscopolamine and the NMDA antagonist AP-5 injected unilaterally into the nucleus accumbens cause mice to rotate in opposite directions

Svensson

Carlsson

1995

J. Neural Transmission

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Previously, we have reported that the NMDA antagonist AP-5, injected unilaterally into the nucleus accumbens of mice, induces ipsilateral rotation in monoaminergically intact mice, but contralateral rotation in monoamine-depleted animals. In this paper we report that the muscarine antagonist methscopolamine, injected unilaterally into the nucleus accumbens, induced predominantly contralateral rotation in monoaminergically intact mice. In monoamine-depleted animals intra-accumbens methscopolamine induced only a weak stimulation of rotational behaviour (not significant), but the direction of the rotation was exclusively contralateral, and the animals showed contralateral body deviation. Moreover, when these animals received additional treatment with the alpha-adrenergic agonist clonidine, which potentiates the motor effects of cholinergic antagonists in monoamine-depleted mice (Carlsson et al., 1991), a clear-cut contralateral rotation was induced. The observed behavioural effects are discussed in relation to the positive and negative feedback circuits, which link the nucleus accumbens with the cerebral cortex and thalamus. In previous papers, we have suggested that the ipsilateral rotation induced by AP-5 is mediated primarily by the positive feedback circuit, whereas the AP-5-induced contralateral rotation is due to interference with primarily the negative feedback circuit. Applying this reasoning to the rotational effects of methscopolamine, it seems that methscopolamine interferes primarily with the negative feedback circuit.

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“…[32][33][34][35][36] However, other studies have demonstrated that intrastriatal injection of the same NMDA receptor antagonists or NMDA receptors that mediate their effects through the same mechanism do not stimulate locomotor activity in animal models of Parkinson's disease. 33,34,[37][38][39][40] The reason behind these discrepancies may lie in the precise site of injection within the striatum and also the type of NMDA receptor antagonist administered. Similar disparities have arisen following systemic administration of NMDA receptor antagonists in animal models of Parkinson's disease.…”

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confidence: 99%

Characterisation of striatal NMDA receptors involved in the generation of parkinsonian symptoms: Intrastriatal microinjection studies in the 6‐OHDA‐lesioned rat

Nash

Brotchie

2002

Movement Disorders

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Treatments for Parkinson's disease based on replacement of lost dopamine have several problems. Following loss of dopamine, enhanced N-methyl-D-aspartate (NMDA) receptor-mediated transmission in the striatum is thought to be part of the cascade of events leading to the generation of parkinsonian symptoms. We determined the localisation and pharmacological characteristics of NMDA receptors that play a role in generating parkinsonian symptoms within the striatum. Rats were lesioned unilaterally with 6-hydroxydopamine (6-OHDA), and cannulae implanted bilaterally to allow injection of a range of NMDA receptor antagonists at different striatal sites. When injected rostrally into the dopamine-depleted striatum, the glycine site partial agonist, (+)-HA-966 (44-400 nmol) caused a dose-dependent contraversive rotational response consistent with an antiparkinsonian action. (+)-HA-966 (400 nmol) had no effect when infused into more caudal regions of the dopamine-depleted striatum, or following injection into any striatal region on the dopamine-intact side. To determine the pharmacological profile of NMDA receptors involved in inducing parkinsonism in 6-OHDA-lesioned rats, a range of NMDA receptor antagonists was infused directly into the rostral striatum. Ifenprodil (100 nmol) and 7-chlorokynurenate (37 nmol), but not MK-801 (15 nmol) or D-APV (25 nmol) elicited a dramatic rotational response when injected into the dopamine-depleted striatum. This pharmacological profile is not consistent with an effect mediated via blocking NR2B-containing NMDA receptors. The effect of intrastriatal injection of ifenprodil was increased in animals previously treated with levodopa (L-dopa) methyl ester. This was seen as an increase in on-time and in peak rotational response. We propose that stimulation of NR2B-containing NMDA receptors in the rostral striatum underlies the generation of parkinsonian symptoms. These studies are in line with previous findings suggesting that administration of NR2B-selective NMDA receptor antagonists may be therapeutically beneficial for parkinsonian patients, when given de novo and following L-dopa treatment.

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Interaction between glutamatergic and dopaminergic tone in the nucleus accumbens of mice: evidence for a dual glutamatergic function with respect to psychomotor control

Cited by 41 publications

References 8 publications

Crucial role of the accumbens nucleus in the neurotransmitter interactions regulating motor control in mice

Crucial role of the accumbens nucleus in the neurotransmitter interactions regulating motor control in mice

The muscarine antagonist methscopolamine and the NMDA antagonist AP-5 injected unilaterally into the nucleus accumbens cause mice to rotate in opposite directions

Characterisation of striatal NMDA receptors involved in the generation of parkinsonian symptoms: Intrastriatal microinjection studies in the 6‐OHDA‐lesioned rat

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