Rodent Models of ADHD

Fan, Xionglin; Bruno, Kristy J.; Hess, Ellen J.

doi:10.1007/7854_2011_121

Cited by 39 publications

(22 citation statements)

References 129 publications

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“…23 The 4 most extensively studied animal models of ADHD are the neonatal 6-hydroxydopaminelesioned rat, the coloboma mutant mouse, the dopamine transporter-knockout/down mouse, and the spontaneously hypertensive rat. The behavioral and neurochemical features of each of these models, with a focus on the features that they share, have been recently reviewed by Fan et al 24 The Lenti-dopamine transporter is an innovative and promising animal model, developed through brain inoculation of selfinactivating, regulatable lentiviruses, targeting the dopamine transporter gene and protein expression. 25,26 Specifically, these animals could serve as a model for symptoms observed in cases of comorbidity between ADHD and pathologic gambling.…”

Section: Rodent Models Of Adhdmentioning

confidence: 99%

MR Imaging-Detectable Metabolic Alterations in Attention Deficit/Hyperactivity Disorder: From Preclinical to Clinical Studies

Altabella

Zoratto

Adriani

et al. 2014

American Journal of Neuroradiology

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MR spectroscopy represents one of the most suitable in vivo tool to assess neurochemical dysfunction in several brain disorders, including attention deficit/hyperactivity disorder. This is the most common neuropsychiatric disorder in childhood and adolescence, which persists into adulthood (in approximately 30%-50% of cases). In past years, many studies have applied different MR spectroscopy techniques to investigate the pathogenesis and effect of conventional treatments. In this article, we review the most recent clinical and preclinical MR spectroscopy results on subjects with attention deficit/hyperactivity disorder and animal models, from childhood to adulthood. We found that the most investigated brain regions were the (pre)frontal lobes and striatum, both involved in the frontostriatal circuits and networks that are known to be impaired in this pathology. Neurometabolite alterations were detected in several regions: the NAA, choline, and glutamatergic compounds. The creatine pool was also altered when an absolute quantitative protocol was adopted. In particular, glutamate was increased in children with attention deficit/hyperactivity disorder, and this can apparently be reversed by methylphenidate treatment. The main difficulties in reviewing MR spectroscopy studies were in the nonhomogeneity of the analyzed subjects, the variety of the investigated brain regions, and also the use of different MR spectroscopy techniques. As for possible improvements in future studies, we recommend the use of standardized protocols and the analysis of other brain regions of particular interest for attention deficit hyperactivity disorder, like the hippocampus, limbic structures, thalamus, and cerebellum.ABBREVIATIONS: ACC ϭ anterior cingulate cortex; ADHD ϭ attention deficit/hyperactivity disorder; Cho ϭ total choline (phosphorylcholine ϩ glycerolphosphorylcholine); GABA ϭ ␥-aminobutyric acid; PFC ϭ prefrontal cortex; PRESS ϭ point-resolved spectroscopy sequence; tCr ϭ total creatine (creatine ϩ phosphorylcreatine) A ttention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disease in children and adolescents. Marked differences in the ADHD prevalence are thought to exist among countries. In fact, the estimated prevalence is 4%-7% in the United States and 1%-3% in Europe.1 ADHD, which is 2-4 times more frequent in males than in females, is characterized by traits of inattention, impulsivity, and motor hyperactivity. These can significantly impact many aspects of behavior in children and adolescents and can affect their performance, both at school and at home. The symptoms of ADHD have a negative impact on the individual throughout childhood, adolescence, and well into adult life, especially if not managed optimally. In approximately 80% of children with ADHD, symptoms persist into adolescence and may persist into adulthood in approximately 30%-50% of cases. ADHD adolescents and adults retain from infancy the traits of inattention and impulsivity. Moreover, they start to show a propensity for ...

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Section: Rodent Models Of Adhdmentioning

confidence: 99%

MR Imaging-Detectable Metabolic Alterations in Attention Deficit/Hyperactivity Disorder: From Preclinical to Clinical Studies

Altabella

Zoratto

Adriani

et al. 2014

American Journal of Neuroradiology

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“…It is also true for rodents, since dopamine depletion by 6-hydroxydopamine (6-OHDA) in adult rats causes akinesia (37)(38)(39). However, neonatal 6-OHDA treatment in rats causes hyperactivity (40)(41)(42).…”

Section: Figurementioning

confidence: 99%

Dopamine dysregulation in a mouse model of paroxysmal nonkinesigenic dyskinesia

Lee¹,

Nakayama²,

Xu³

et al. 2012

J. Clin. Invest.

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Paroxysmal nonkinesigenic dyskinesia (PNKD) is an autosomal dominant episodic movement disorder.Patients have episodes that last 1 to 4 hours and are precipitated by alcohol, coffee, and stress. Previous research has shown that mutations in an uncharacterized gene on chromosome 2q33-q35 (which is termed PNKD) are responsible for PNKD. Here, we report the generation of antibodies specific for the PNKD protein and show that it is widely expressed in the mouse brain, exclusively in neurons. One PNKD isoform is a membrane-associated protein. Transgenic mice carrying mutations in the mouse Pnkd locus equivalent to those found in patients with PNKD recapitulated the human PNKD phenotype. Staining for c-fos demonstrated that administration of alcohol or caffeine induced neuronal activity in the basal ganglia in these mice. They also showed nigrostriatal neurotransmission deficits that were manifested by reduced extracellular dopamine levels in the striatum and a proportional increase of dopamine release in response to caffeine and ethanol treatment. These findings support the hypothesis that the PNKD protein functions to modulate striatal neurotransmitter release in response to stress and other precipitating factors. IntroductionThe paroxysmal dyskinesias consist of clinically and genetically distinct phenotypes, including paroxysmal kinesigenic dyskinesia, paroxysmal exercise-induced dyskinesia, and paroxysmal nonkinesigenic dyskinesia (PNKD) (1, 2). PNKD is a highly penetrant autosomal dominant disorder in which individuals have 1- to 4-hour attacks consisting of dystonia and choreoathetosis (3). These attacks can be induced reliably by administration of caffeine or alcohol and frequently when patients are stressed. The causative gene was mapped to chromosome 2q33-q35 (4, 5), and mutations in the PNKD gene (formerly called MR-1) were subsequently identified in PNKD families (6)(7)(8)(9)(10).The PNKD gene has at least 3 alternate splice forms, which encode proteins of 385, 361, and 142 amino acids. The long isoform of PNKD (PNKD-L) is specifically expressed in CNS, while the medium isoform (PNKD-M) and short isoform (PNKD-S) are ubiquitously expressed (7). Two missense mutations (Ala to Val) located at amino acids 7 or 9 of PNKD-L and PNKD-S were found in most patients, and a third mutation (Ala to Pro) at position 33 was reported in 1 family (11). Both PNKD-L and PNKD-M have a putative catalytic domain that is homologous to hydroxyacylglutathione hydrolase (HAGH), a member of the zinc metallo-hydrolase enzyme family, which contains β-lactamase domains. HAGH functions in a pathway to detoxify methylglyoxal, a by-product of oxidative stress (12). The normal role of PNKD in cells and the contribution of mutations to pathophysiology of PNKD are not known.Dyskinesia is seen with many genetic and acquired disorders of the brain. Theoretically, such hyperkinetic movements could have their genesis in the basal ganglia, the cerebellum, or even in the cortex. Having cloned the gene and shown by in situ hybridization that it is...

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“…Transcriptional profiling analysis in animal models of disorders can also provide an important tool for dissecting genetic involvement in behavioral phenotypes [9]. Of all animal models of ADHD, the spontaneously hypertensive rat (SHR) is the most frequently used [10,11]. In particular, the SHR/NCrl substrain has been the best validated ADHD animal model as it exhibits all the behavioral characteristics of ADHD such as impaired sustained attention without obvious sensory problems, motor impulsivity, and hyperactivity in comparison with controls [12].…”

Section: Introductionmentioning

confidence: 99%