Guanfacine produces differential effects in frontal cortex compared with striatum: assessed by phMRI BOLD contrast

Easton, Neil; Shah, Yasmene B.; Marshall, Fiona H.; Fone, Kevin C. F.; Marsden, C.A.

doi:10.1007/s00213-006-0558-1

Cited by 36 publications

(20 citation statements)

References 76 publications

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“…By simultaneous application of fMRI and electrophysiological recordings, some authors have associated negative BOLD responses with local decreases in neuronal activity (Shmuel et al 2006). These results would be in agreement with Easton and co-workers who also found widespread negative BOLD in STR and NAcc of young adult rats treated with guanfacine or atomoxetine (Easton et al 2007a;Easton et al 2006). These drugs may act on the prefrontal cortex, which in turn could exert its inhibitory control on subcortical brain regions.…”

Section: Discussionsupporting

confidence: 84%

“…Other physiological parameters, like systemic blood pressure or haemogas composition, may specifically affect the BOLD signal and might represent a 'bias'. Such parameters were monitored in our rats and were in agreement with those found by Easton and co-workers in rats of comparable body weight (Easton et al 2006). Despite the expected age-dependent basal differences found for HR and pCO 2 , all values still remained within the physiological range (Rioja et al 2006;Sharp and LaRegina 1998).…”

Section: Discussionsupporting

confidence: 65%

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Peculiar response to methylphenidate in adolescent compared to adult rats: a phMRI study

et al. 2008

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The present findings highlight the utility of phMRI in animal models. The peculiar negative BOLD effect found in adolescent rats may be suggestive of a reduced cerebro-vascular feedback and/or an increased MPH-induced neuronal activation. Data are relevant for a better understanding of brain/behavioural regulation during adolescent development. Moreover, a greater understanding of the differences between adult and adolescent drug responses will aid in the development of a more appropriate age-specific treatment strategy.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 65%

Peculiar response to methylphenidate in adolescent compared to adult rats: a phMRI study

et al. 2008

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“…Some authors have associated negative BOLD responses with local decreases in neuronal activity (Shmuel et al 2006). These results agree with those of Easton and coworkers who also found widespread negative BOLD in the striatum of young adult rats (Easton et al 2006(Easton et al , 2007 treated with guanfacine or atomoxetine, two alternative drugs for ADHD therapy. As with guanfacine and atomoxetine, MPH appears to have the ability to "turn down" striatal activity in the immature brain of adolescent and young adult rats, which may account for its beneficial modulatory role in the treatment of ADHD (Levy and Swanson 2001).…”

Section: Pharmacological Imaging Of Mph In the Adolescent Forebrainsupporting

confidence: 89%

Brain Processes in Discounting: Consequences of Adolescent Methylphenidate Exposure

Adriani

Zoratto

Laviola

2011

Behavioral Neuroscience of Attention Deficit Hyperactivity Disorder and Its Treatment

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Traits of inattention, impulsivity, and motor hyperactivity characterize children diagnosed with attention-deficit/hyperactivity disorder (ADHD), whose inhibitory control is reduced. In animal models, crucial developmental phases or experimental transgenic conditions account for peculiarities, such as sensation-seeking and risk-taking behaviors, and reproduce the beneficial effects of psychostimulants. An "impulsive" behavioral profile appears to emerge more extremely in rats when forebrain dopamine (DA) systems undergo remodeling, as in adolescence, or with experimental manipulation tapping onto the dopamine transporter (DAT). Ritalin(®) (methylphenidate, MPH), a DAT-blocking drug, is prescribed for ADHD therapy but is also widely abused by human adolescents. Administration of MPH during rats' adolescence causes a long-term modulation of their self-control, in terms of reduced intolerance to delay and diminished proneness for risk when reward is uncertain. Exactly the opposite profile emerges when exogenous alteration of DAT levels is achieved via lentiviral transfection. Both adolescent MPH exposure and DAT-targeting transfection lead to enduring hyperfunction of dorsal striatum and hypofunction of ventral striatum. Together with upregulation of prefronto-cortical phospho-creatine, striatal upregulation of selected genes (like serotonin 7 receptor gene) suggests that enhanced inhibitory control is generated by adolescent MPH exposure. Operant tasks, which assess the balance between motivational drives and inhibitory self-control, are thus useful for investigating reward-discounting processes and their modulation by DAT-targeting tools. In summary, due to the complexity of human studies, preclinical investigations of rodent models are necessary to understand better both the neurobiology of ADHD-like symptoms' etiology and the long-term therapeutic safety of adolescent MPH exposure.

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“…In animals, suboptimal prefrontal NE results in a phenotype similar to ADHD, and NE agonists and antagonists enhance and reduce working memory function, respectively [reviewed in Brennan and Arnsten, 2008]. Further, pharmacological fMRI studies in rats showed reduction in striatal structures and increase in frontal cortex, relative to activation without atomoxetine [Easton et al, 2006[Easton et al, , 2007; there are no human fMRI studies with these medications. Thus, efficacy of NE agonists for ADHD is likely to be mediated by modulating prefrontal-striatal functional relationships.…”

Section: Effects Of Medicationmentioning

confidence: 97%

Cognitive neuroscience of Attention Deficit Hyperactivity Disorder: Current status and working hypotheses

Vaidya

Stollstorff

2008

Dev Disabil Res Revs

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Cognitive neuroscience studies of Attention Deficit Hyperactivity Disorder (ADHD) suggest multiple loci of pathology with respect to both cognitive domains and neural circuitry. Cognitive deficits extend beyond executive functioning to include spatial, temporal, and lower-level "nonexecutive" functions. Atypical functional anatomy extends beyond frontostriatal circuits to include posterior cortices, limbic regions, and the cerebellum. Pathophysiology includes dopaminergic as well as noradrenergic neurotransmitter systems. We review the major insights gained from functional brain imaging studies in ADHD and discuss working hypotheses regarding their neurochemical underpinnings.

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Guanfacine produces differential effects in frontal cortex compared with striatum: assessed by phMRI BOLD contrast

Cited by 36 publications

References 76 publications

Peculiar response to methylphenidate in adolescent compared to adult rats: a phMRI study

Peculiar response to methylphenidate in adolescent compared to adult rats: a phMRI study

Brain Processes in Discounting: Consequences of Adolescent Methylphenidate Exposure

Cognitive neuroscience of Attention Deficit Hyperactivity Disorder: Current status and working hypotheses

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