Atomoxetine Enhances a Short-Term Model of Plasticity in Humans

Foster, Donald J.; Good, David C.; Fowlkes, Allison; Sawaki, Lumy

doi:10.1016/j.apmr.2005.08.131

Cited by 30 publications

(18 citation statements)

References 42 publications

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“…While significant improvements in learning and memory are not always found (Rie et al 1976;Swanson et al 1991), a recent review (Pietrzak et al 2006) suggested that improvements in short-and long-term memory are seen in 58% of studies following methylphenidate treatment, and Swanson et al (1991) suggest that improvements are not seen in all cases, as doses are calibrated according to behavior and not cognition. Our results are also in line with the recent study showing that atomoxetine, a selective noradrenalin reuptake inhibitor, also used for treating ADHD, can enhance performance on a task aimed at modeling plasticity (Foster et al 2006).…”

supporting

confidence: 81%

Methylphenidate amplifies long-term plasticity in the hippocampus via noradrenergic mechanisms

Dommett¹,

Henderson²,

Westwell³

et al. 2008

Learn. Mem.

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Methylphenidate treatment is used for Attention Deficit Hyperactivity Disorder and can improve learning and memory. Previously, improvements were considered a by-product of increased attention; however, we hypothesize that methylphenidate directly alters mechanisms underlying learning and memory, and therefore examined its effects on hippocampal long-term potentiation and long-term depression. Methylphenidate enhanced both mechanisms in the absence of presynaptic changes and in a noradrenalin ␤-receptor-dependent manner. These findings can explain both the improved learning and memory and decreased learning selectivity found with methylphenidate treatment and constitute the first demonstration of direct actions of methylphenidate on mechanisms implicated in cognition.Attention Deficit Hyperactivity Disorder (ADHD) affects 8%-12% of children (Biederman and Faraone 2005) and is characterized by inattention, hyperactivity, and impulsivity. Consequences of the disorder include poorer academic performance, employment records, social relationships, and a higher risk of drug abuse (Doggett 2004). While behavioral, cognitive, and psychosocial therapies exist for ADHD, they are often ineffective unless combined with pharmacological treatment , the most common of which is the psychostimulant, methylphenidate (Ritalin, Concerta). Methylphenidate is known to increase extracellular dopamine and noradrenalin Segal 1997, 2002), but not serotonin (Kuczenski and Segal 1997) suggesting that therapeutic efficacy relates to alterations in dopamine and noradrenalin. Despite knowledge of these neurochemical effects, the mechanisms contributing to the effectiveness of methylphenidate are unclear (Safer and Allen 1989; National Institutes of Health Consensus Development Conference Statement 2000;Greenhill 2001).One clue to mechanisms of efficacy can be found at a behavioral level, where methylphenidate improves academic performance (Yang et al. 2004;McGough et al. 2006), working (Wright and White 2003) and visual (Rhodes et al. 2004) memory, nonverbal (O'Toole et al. 1997) and visuospatial (Bedard et al. 2004) learning, and reading skills (Keulers et al. 2007), which may explain why, in addition to its medicinal use, it is used illegally by healthy students to aid study (Teter et al. 2006). Despite evidence of methylphenidate-induced changes in learning and memory, the mechanisms underlying these changes have received little focus and are commonly assumed to be a by-product of improved attention. However, we suggest that these findings are the result of direct actions of methylphenidate on learning and memory mechanisms.In support of this hypothesis, methylphenidate has been shown to increase hippocampal noradrenalin in vivo (Kuczenski and Segal 2002), and such changes are known to impact on plasticity such as long-term potentiation (LTP) and long-term depression (LTD) (Hopkins and Johnston 1984;Izumi et al. 1992;Sah and Bekkers 1996;Thomas et al. 1996;Izumi and Zorumski 1999;Schimanski et al. 2007;Lin et al. 2008), both of which a...

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supporting

confidence: 81%

Methylphenidate amplifies long-term plasticity in the hippocampus via noradrenergic mechanisms

Dommett¹,

Henderson²,

Westwell³

et al. 2008

Learn. Mem.

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“…Thus, while NA is clearly implicated in emotional memory, differential effects have been reported as a function of stimulus valence and this remains an important area of investigation. In addition to effects on emotional long-term memory and priming, facilitating effects of reboxetine and atomoxetine on motor memory (learning of finger movement sequences) have been demonstrated that might also be arousal-dependent (Plewnia et al 2004;Foster et al 2006). …”

Section: Discussionmentioning

confidence: 96%

Noradrenergic modulation of working memory and emotional memory in humans

et al. 2006

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Improved understanding of coupling between NA, cortico-subcortical circuitry and human mnemonic functions will suggest novel therapeutic directions for the treatment of neuropsychiatric conditions, such as attention deficit hyperactivity disorder and post-traumatic stress disorder. Future research directions are discussed in relation to neuroimaging techniques, functional central nervous system polymorphisms and study designs.

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“…The prefrontal cortex, believed to be important for various types of cognitive flexibility (Vikki et al, 1992;Karnath and Wallesch, 1992;Eslinger and Grattan, 1993;Duncan et al, 1995;Robbins, 2007), has afferent projections to the locus coeruleus in primates (Arnsten and GoldmanRakic, 1984), which contains a majority of the noradrenergic neurons in the central nervous system and sends extensive efferents throughout the brain (Barnes and Pompeiano, 1991). A range of other cognitive effects have also been described with noradrenergic agents, including effects on motor learning (Foster et al, 2006), response inhibition (Chamberlain et al, 2006a), working memory, and emotional memory (Chamberlain et al, 2006b).…”

Section: Mechanism Of the Effects Of The Noradrenergic System On Cognmentioning

confidence: 96%

The Role of the Noradrenergic System in Autism Spectrum Disorders

Beversdorf

2010

The Neurochemical Basis of Autism

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Atomoxetine Enhances a Short-Term Model of Plasticity in Humans

Cited by 30 publications

References 42 publications

Methylphenidate amplifies long-term plasticity in the hippocampus via noradrenergic mechanisms

Methylphenidate amplifies long-term plasticity in the hippocampus via noradrenergic mechanisms

Noradrenergic modulation of working memory and emotional memory in humans

The Role of the Noradrenergic System in Autism Spectrum Disorders

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