Hypertrophic A10 dopamine neurones in a rat model of attention-deficit hyperactivity disorder (ADHD)

Viggiano, D.; Sadile, Adolfo G.

doi:10.1097/00001756-200011270-00018

Cited by 22 publications

(13 citation statements)

References 7 publications

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“…Furthermore, the cellular and molecular mechanisms that underlie the increased dopaminergic activity in these mice also remain unknown. Previous studies have shown that changes in dopamine neuronal size are associated with differences in reward-related behavior, depression-related behavior, and hyperactivity (Krishnan et al, 2008a;Russo et al, 2007;Viggiano and Sadile, 2000). Here we find that changes in dopamine cell morphology and neuronal activity are important for the expression of hyperactivity and anxiety-related phenotypes of the ClockD19 mice, and that chronic lithium likely restores proper behavior in part through the modulation of this system.…”

Section: Introductionsupporting

confidence: 64%

Specific Role of VTA Dopamine Neuronal Firing Rates and Morphology in the Reversal of Anxiety-Related, but not Depression-Related Behavior in the ClockΔ19 Mouse Model of Mania

Coque

Mukherjee

Cao

et al. 2011

Neuropsychopharmacol

112

100

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Lithium has been used extensively for mood stabilization, and it is particularly efficacious in the treatment of bipolar mania. Like other drugs used in the treatment of psychiatric diseases, it has little effect on the mood of healthy individuals. Our previous studies found that mice with a mutation in the Clock gene (ClockD19) have a complete behavioral profile that is very similar to human mania, which can be reversed with chronic lithium treatment. However, the cellular and physiological effects that underlie its targeted therapeutic efficacy remain unknown. Here we find that ClockD19 mice have an increase in dopaminergic activity in the ventral tegmental area (VTA), and that lithium treatment selectively reduces the firing rate in the mutant mice with no effect on activity in wild-type mice. Furthermore, lithium treatment reduces nucleus accumbens (NAc) dopamine levels selectively in the mutant mice. The increased dopaminergic activity in the Clock mutants is associated with cell volume changes in dopamine neurons, which are also rescued by lithium treatment. To determine the role of dopaminergic activity and morphological changes in dopamine neurons in manic-like behavior, we manipulated the excitability of these neurons by overexpressing an inwardly rectifying potassium channel subunit (Kir2.1) selectively in the VTA of ClockD19 mice and wild-type mice using viral-mediated gene transfer. Introduction of this channel mimics the effects of lithium treatment on the firing rate of dopamine neurons in ClockD19 mice and leads to a similar change in dopamine cell volume. Furthermore, reduction of dopaminergic firing rates in ClockD19 animals results in a normalization of locomotor-and anxiety-related behavior that is very similar to lithium treatment; however, it is not sufficient to reverse depression-related behavior. These results suggest that abnormalities in dopamine cell firing and associated morphology underlie alterations in anxiety-related behavior in bipolar mania, and that the therapeutic effects of lithium come from a reversal of these abnormal phenotypes.

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Section: Introductionsupporting

confidence: 64%

Specific Role of VTA Dopamine Neuronal Firing Rates and Morphology in the Reversal of Anxiety-Related, but not Depression-Related Behavior in the ClockΔ19 Mouse Model of Mania

Coque

Mukherjee

Cao

et al. 2011

Neuropsychopharmacol

112

100

View full text Add to dashboard Cite

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“…This view is supported by the increase in TH activity found in another animal model of ADHD, the Naples highexcitability (NHE) rat (Viggiano et al, 2000(Viggiano et al, , 2002. If one assumes that the SHR phenotype is a model of ADHD, then the higher dopamine basal concentration found in the NAc of SHR as compared with WKY rats (Carboni et (Kumai et al, 1996) and TH gene expression (Reja et al, 2002) in the medulla oblongata of SHR rats.…”

Section: Discussionmentioning

confidence: 99%

Experimental Investigations on Dopamine Transmission Can Provide Clues on the Mechanism of the Therapeutic Effect of Amphetamine and Methylphenidate in ADHD

Carboni

Silvagni

2004

Neural Plasticity

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“…For example, tyrosine hydroxylase, DAT and D 2 receptor mRNA are hyperexpressed in the PFC, while the D 1 receptor is down-regulated. No such changes have been reported for the striatum (Viggiano et al 2002a(Viggiano et al , b, 2003aViggiano and Sadile 2000).…”

Section: The Coloboma Mutant Mousementioning

confidence: 94%

Animal models of attention deficit/hyperactivity disorder (ADHD): a critical review

Sontag

Tucha

Walitza

et al. 2010

ADHD Atten Def Hyp Disord

104

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Attention deficit/hyperactivity disorder (ADHD) involves clinically heterogeneous problems including attention deficits, behavioural hyperactivity and impulsivity. Several animal models of ADHD have been proposed, ranging from models with neurotoxic lesions to genetically manipulated animals. An ADHD model is supposed to show phenomenological similarities with the disorder, i.e. it should mimic the three core symptoms (face validity). A model should also conform to an established or hypothesized pathophysiological basis of the disorder (construct validity).Finally, an animal model should be able to predict previously unknown aspects of the neurobiology of ADHD or to provide potential new treatments (predictive validity). The currently proposed models are heterogeneous with regard to their pathophysiological alterations and their ability to mimic behavioural symptoms and to predict response to medication. This might reflect the heterogeneous nature of ADHD. Since the knowledge about the biology of ADHD from human studies is limited, one cannot at present decide which model best represents ADHD or certain ADHD subtypes. Animal models with good face and predictive validity may be useful for investigations of the underlying biological substrates of ADHD. At present, the models in use should be described as animal models of ADHD-like symptoms rather than models of ADHD.

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Hypertrophic A10 dopamine neurones in a rat model of attention-deficit hyperactivity disorder (ADHD)

Cited by 22 publications

References 7 publications

Specific Role of VTA Dopamine Neuronal Firing Rates and Morphology in the Reversal of Anxiety-Related, but not Depression-Related Behavior in the ClockΔ19 Mouse Model of Mania

Specific Role of VTA Dopamine Neuronal Firing Rates and Morphology in the Reversal of Anxiety-Related, but not Depression-Related Behavior in the ClockΔ19 Mouse Model of Mania

Experimental Investigations on Dopamine Transmission Can Provide Clues on the Mechanism of the Therapeutic Effect of Amphetamine and Methylphenidate in ADHD

Animal models of attention deficit/hyperactivity disorder (ADHD): a critical review

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