Nur77 and retinoid X receptors: crucial factors in dopamine-related neuroadaptation

Lévesque, Daniel; Rouillard, Claude

doi:10.1016/j.tins.2006.11.006

Cited by 87 publications

(68 citation statements)

References 72 publications

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“…C-fos and Nur77 are immediate early genes that rapidly respond to changes in cell activity. Both genes transform acute cellular events into lasting changes in cell function by regulating the transcription of late-onset genes (Levesque and Rouillard, 2007;Robertson et al, 1991). Thus, our findings indicate that continuous exposure to antipsychotic medication induces lasting changes in both the behavioral and neurobiological impact of amphetamine.…”

Section: Discussionmentioning

confidence: 70%

Continuous, but not Intermittent, Antipsychotic Drug Delivery Intensifies the Pursuit of Reward Cues

Bédard

Maheux

Lévesque

et al. 2011

Neuropsychopharmacol

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Chronic exposure to antipsychotic medications can persistently change brain dopamine systems. Most studies on the functional significance of these neural changes have focused on motor behavior and few have addressed how long-term antipsychotic treatment might influence dopamine-mediated reward function. We asked, therefore, whether a clinically relevant antipsychotic treatment regimen would alter the incentive motivational properties of a reward cue. We assessed the ability of a Pavlovian-conditioned stimulus to function as a conditioned reward, as well as to elicit approach behavior in rats treated with haloperidol, either continuously (achieved via subcutaneous osmotic minipump) or intermittently (achieved via daily subcutaneous injections). Continuous, but not intermittent, treatment enhanced the ability of amphetamine to potentiate the conditioned reinforcing effects of a cue associated with water. This effect was not related to differences in the ability to attribute predictive value to a conditioned stimulus (as measured by conditioned approach behavior), but was potentially linked to the development of behavioral supersensitivity to amphetamine and to augmented amphetamine-induced immediate early-gene expression (c-fos and Nur77) in dorsal striatopallidal and striatonigral cells. By enhancing the ability of reward cues to control behavior and by intensifying dopamine-mediated striatopallidal and striatonigral cell activity, standard (ie, continuous) antipsychotic treatment regimens might exacerbate drug-seeking and drug-taking behavior in schizophrenia. Achieving regular but transiently high antipsychotic levels in the brain (as modeled in the intermittent condition) might be a viable option to prevent these changes. This possibility should be explored in the clinic.

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Section: Discussionmentioning

confidence: 70%

Continuous, but not Intermittent, Antipsychotic Drug Delivery Intensifies the Pursuit of Reward Cues

Bédard

Maheux

Lévesque

et al. 2011

Neuropsychopharmacol

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“…Second, modulations of Nur77 expression can be observed after chronic denervation and prolonged dopamine replacement therapy, indicating that these modulations do not desensitized over time. Third, by promoting the formation of the Nur77/RXR transcriptional complex (Lévesque and Rouillard, 2007), Nur77 can be viewed as a molecular switch that renders the striatum responsive to RXR agonists, making Nur77-dependent transcriptional activity and RXR an attractive new pharmacological entity aims to control LIDs. We have shown that Nur77 gene ablation alters the modulation of striatal neuropeptides, like neurotensin, normally observed following denervation and L-DOPA therapy .…”

Section: Discussionmentioning

confidence: 99%

“…Basal levels of Nur77 are found in most of dopaminoceptive structures such as the striatum, nucleus accumbens, olfactory tubercle and prefrontal cortex (Xiao et al, 1996;Zetterström et al, 1996b). Its expression is strongly modulated after manipulation of dopamine neurotransmission, for review see (Lévesque and Rouillard, 2007). Unilateral denervation induced by local injection of 6-hydroxydopamine (6-OHDA) in rats produces a complex regulation of Nur77 in the striatum (St-Hilaire et al, 2005;St-Hilaire et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Nur77 mRNA levels and L-Dopa-induced dyskinesias in MPTP monkeys treated with docosahexaenoic acid

Mahmoudi

Samadi

Gilbert

et al. 2009

Neurobiology of Disease

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We have previously shown that docosahexaenoic acid (DHA) significantly reduced L-Dopainduced dyskinesia (LID) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys (Samadi et al., Ann. Neurol. 59:282-288, 2006). In the present study, we measured for the first time mRNA levels of Nur77, an orphan nuclear receptor that participates to adaptive and/or aberrant dopamine-related behaviors, and retinoid X receptor γ1 (RXRγ1), a putative brain receptor for DHA and transcriptional partner of Nur77, in MPTP monkeys treated with L-Dopa and DHA. The RXRγ1 mRNA is strongly expressed in monkey caudate nucleus and putamen, but no change in levels of RXRγ1 was observed following MPTP and L-Dopa treatments. On the other hand, denervation reduced Nur77 mRNA levels, whereas chronic L-Dopa treatment strongly induced Nur77 transcripts. These modulations are taking placed in substance P positive cells and are associated with both caudate-putamen matrix and striosome compartments. Interestingly, combination of L-Dopa with DHA further increases Nur77 mRNA levels in the anterior caudateputamen, and mainly in striosomes. This is accompanied by a significant inverse correlation between Nur77 mRNA levels and dyskinetic scores. Taken together, our results show that Nur77 expression is modulated following dopamine denervation and chronic L-Dopa therapy in a nonhuman primate model of Parkinson's disease, and suggest that strong modulation of Nur77 expression might be linked to a reduced risk to develop LIDs.

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“…The RXR heterodimerizes with Nurr1, and promotes differentiation and survival of dopamine neurons, and modulates dopamine synthesis and function during both development and adult life [30,40,41]. Interactions of RXR and Nur77 also modulate dopaminergic function [20].…”

Section: Introductionmentioning

confidence: 99%

Reduced numbers of dopamine neurons in the substantia nigra pars compacta and ventral tegmental area of rats fed an n-3 polyunsaturated fatty acid-deficient diet: A stereological study

Ahmad

Park

Radel

et al. 2008

Neuroscience Letters

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Inadequate dietary n-3 polyunsaturated fatty acid (PUFA) content is associated with altered function of the CNS dopamine systems. In this study, the effects of dietary n-3 PUFA content was determined on dopamine cell number and morphology. Adult (postnatal day 70), male, Long-Evans rats were raised from conception on diets containing adequate (control) or negligible n-3 PUFAs. The number and morphology of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta and ventral tegmental area were determined stereologically. The number of tyrosine hydroxylase-positive cells in rats fed the n-3 PUFA-deficient diet was 33.9% lower in the substantia nigra pars compacta and 33.7% lower in the ventral tegmental area than in those fed the control diet (P<0.05); however, the volume of tyrosine hydroxylase-positive cell bodies was not different between diet groups in either brain region. Rats fed the n-3 PUFA-deficient diet also exhibited dendritic depletion and isolation of tyrosine hydroxylase-positive cells compared to rats fed the control diet, which had clustering of tyrosine hydroxylase-positive cells and extensive dendritic arborization. These findings support a role for n-3 PUFAs in the survival of dopamine neurons and suggest that altered dopamine cell number, as well as function, contributes to the behavioral effects observed in rats raised on n-3 PUFA-deficient diets.

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Nur77 and retinoid X receptors: crucial factors in dopamine-related neuroadaptation

Cited by 87 publications

References 72 publications

Continuous, but not Intermittent, Antipsychotic Drug Delivery Intensifies the Pursuit of Reward Cues

Continuous, but not Intermittent, Antipsychotic Drug Delivery Intensifies the Pursuit of Reward Cues

Nur77 mRNA levels and L-Dopa-induced dyskinesias in MPTP monkeys treated with docosahexaenoic acid

Reduced numbers of dopamine neurons in the substantia nigra pars compacta and ventral tegmental area of rats fed an n-3 polyunsaturated fatty acid-deficient diet: A stereological study

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