Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats

Laplante, François; Zhang, Ziwei; Huppé-Gourgues, Frédéric; Dufresne, M.; Vaucher, Elvire; Sullivan, Ron M.

doi:10.1016/j.neuropharm.2012.07.033

Cited by 22 publications

(23 citation statements)

References 88 publications

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“…ChAT interneuron ablation in the striatum has been previously performed using proteinaceous toxins coupled to specific antibodies (29)(30)(31)(32). Unfortunately, whereas ChAT interneuron ablation was apparent after ChAT-saporin (SAP), we also found reductions in ChAT immunoreactivity, qualitative changes in ChAT cell morphology, and patchy cell loss after treatment with IgG-SAP, even at low doses (Fig.…”

Section: Methodsmentioning

confidence: 85%

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Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

Xu¹,

Kobets²,

Du³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

148

164

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Gilles de la Tourette syndrome (TS) is characterized by tics, which are transiently worsened by stress, acute administration of dopaminergic drugs, and by subtle deficits in motor coordination and sensorimotor gating. It represents the most severe end of a spectrum of tic disorders that, in aggregate, affect ∼5% of the population. Available treatments are frequently inadequate, and the pathophysiology is poorly understood. Postmortem studies have revealed a reduction in specific striatal interneurons, including the large cholinergic interneurons, in severe disease. We tested the hypothesis that this deficit is sufficient to produce aspects of the phenomenology of TS, using a strategy for targeted, specific cell ablation in mice. We achieved ∼50% ablation of the cholinergic interneurons of the striatum, recapitulating the deficit observed in patients postmortem, without any effect on GABAergic markers or on parvalbuminexpressing fast-spiking interneurons. Interneuron ablation in the dorsolateral striatum (DLS), corresponding roughly to the human putamen, led to tic-like stereotypies after either acute stress or D-amphetamine challenge; ablation in the dorsomedial striatum, in contrast, did not. DLS interneuron ablation also led to a deficit in coordination on the rotorod, but not to any abnormalities in prepulse inhibition, a measure of sensorimotor gating. These results support the causal sufficiency of cholinergic interneuron deficits in the DLS to produce some, but not all, of the characteristic symptoms of TS.Tourette sydrome | basal ganglia | interneurons | acetylcholine | animal models

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Section: Methodsmentioning

confidence: 85%

“…We found an immunotoxin that has been used previously to target striatal ChAT interneurons (29)(30)(31)(32) to produce nonspecific effects (Fig. S1).…”

Section: Significancementioning

confidence: 99%

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

Xu¹,

Kobets²,

Du³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

148

164

View full text Add to dashboard Cite

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“…Therefore, in the delayed alternation task, the rat relies on memory of the previous spatial location in order to obtain a reinforcer, whereas the spontaneous alternation task does not require this. Although both tasks have been suggested to involve aspects of the prefrontal cortex, hippocampus, and striatum (Bardullas et al, 2011; Dudchenko et al, 2000; Lapante et al, 2012; Yang et al, 2014), a recent study suggests that the delayed alternation task may not involve the striatum. Hallock et al (2013) revealed that inactivation of the hippocampus but not the striatum impaired performance in the delayed alternation task.…”

Section: Discussionmentioning

confidence: 99%

The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats

Walters

Lansdell

Lookingland

et al. 2015

Toxicology and Applied Pharmacology

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This study sought to investigate the effects of environmentally relevant gestational followed by continued chronic exposure to the herbicide, atrazine, on motor function, cognition, and neurochemical indices of nigrostriatal dopamine (DA) activity in male rats. Dams were treated with 100 µg/kg atrazine, 10 mg/kg atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning, male offspring continued daily vehicle or atrazine gavage treatments for an additional six months. Subjects were tested in a series of behavioral assays, and 24 h after the last treatment, tissue samples from the striatum were analyzed for DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10 mg/kg, this herbicide was found to produce modest disruptions in motor functioning, and at both dose levels it significantly lowered striatal DA and DOPAC concentrations. These results suggest exposures to atrazine have the potential to disrupt nigrostriatal DA neurons and behaviors associated with motor functioning.

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“…The nucleus accumbens is an area that receives mesolimbic dopaminergic projections arising from the ventral tegmental area. Immunohistochemical studies have clearly revealed that cholinergic interneurons are distributed throughout the nucleus accumbens (Bolam, Wainer, & Smith, ; Meredith, Blank, & Groenewegen, ; Phelps, Houser, & Vaughn, ), and enhancement and inhibition of accumbal cholinergic neural activity in experimental animals are known to induce locomotion (Akiyama et al, ; Saigusa et al, ) and cognitive deficits (Laplante et al, ; Laplante, Lappi, & Sullivan, ), respectively.…”

Section: Introductionmentioning

confidence: 99%

In vivo neurochemical evidence that stimulation of accumbal GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

Aono

Watanabe

Ishikawa

et al. 2018

Synapse

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Cholinergic neurons in the nucleus accumbens contain GABAA and GABAB receptors that are thought to inhibit neural activity. We analyzed the roles of GABAA and GABAB receptors in regulating accumbal acetylcholine efflux of freely moving rats using in vivo microdialysis. The effects of GABA receptor ligands on the accumbal dopamine efflux were also analyzed because accumbal cholinergic and dopaminergic neurons could mutually interact. Drugs were applied intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 30–60 min infusions. To monitor basal acetylcholine, a low concentration of physostigmine (50 nM) was added to the perfusate. GABAA receptor agonist muscimol (3 and 30 pmol) induced a dose‐related decrease in accumbal acetylcholine. GABAB receptor agonist baclofen (30 and 300 pmol) also produced a dose‐related decrease in acetylcholine. GABAA receptor antagonist bicuculline (60 pmol) which failed to alter baseline acetylcholine counteracted the muscimol (30 pmol)‐induced decrease in acetylcholine. GABAB receptor antagonist 2‐hydroxysaclofen (12 nmol) which failed to change baseline acetylcholine, counteracted the baclofen (300 pmol)‐induced decrease in acetylcholine. Neither muscimol (30 pmol) nor baclofen (300 pmol) which reduced accumbal acetylcholine altered baseline accumbal dopamine. Neither bicuculline (60 pmol) nor 2‐hydroxysaclofen (12 nmol) also affected the baseline dopamine. These results show that GABAA and GABAB receptors each exert inhibitory roles in the regulation of accumbal cholinergic neural activity. The present results also provides in vivo neurochemical evidence that stimulation of GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats.

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Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats

Cited by 22 publications

References 88 publications

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats

In vivo neurochemical evidence that stimulation of accumbal GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

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Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats

Cited by 22 publications

References 88 publications

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

The effects of gestational and chronic atrazine exposure on motor behaviors and striatal dopamine in male Sprague-Dawley rats

In vivo neurochemical evidence that stimulation of accumbal GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

Contact Info

Product

Resources

About

In vivo neurochemical evidence that stimulation of accumbal GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats