Effects of Long-Term Atomoxetine Treatment for Young Children With Attention-Deficit/Hyperactivity Disorder

Kratochvil, Christopher J.; Wilens, Timothy E.; Greenhill, Laurence L.; Gao, Haitao; Baker, Kurt D.; Feldman, Peter D.; Gelowitz, Douglas L.

doi:10.1097/01.chi.0000222788.34229.68

Cited by 133 publications

(98 citation statements)

References 28 publications

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“…We therefore performed a pharmacological characterization of the effects of methylphenidate on social play. The noradrenaline reuptake inhibitor atomoxetine (Strattera s ), which is also used in the treatment of ADHD (Spencer et al, 2002;Michelson et al, 2003;Kratochvil et al, 2006), suppressed pinning ( Figure 4a). However, neither the dopamine reuptake inhibitor GBR-12909 (Figure 4b) nor the dopamine receptor agonist apomorphine (Figure 4c) inhibited social play.…”

Section: Methylphenidate Suppresses Social Play Through A-2 Adrenocepmentioning

confidence: 99%

Methylphenidate Disrupts Social Play Behavior in Adolescent Rats

Vanderschuren

Trezza

Griffioen-Roose

et al. 2008

Neuropsychopharmacol

144

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Methylphenidate is the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), but its mechanism of action is incompletely understood. The cognitive effects of methylphenidate have been extensively studied, but little is known about its effects on spontaneous social behavior. During adolescence, rats display a characteristic, highly vigorous form of social behavior, termed social play behavior, which is of critical importance for social and cognitive development. We investigated the neurobehavioral mechanisms by which methylphenidate affects social play behavior in rats. Methylphenidate (0.3-3.0 mg/kg, s.c. or p.o.) abolished social play behavior, without altering general social interest. This effect of methylphenidate did not depend upon the baseline level of social play and was not secondary to changes in locomotion. Furthermore, the play-suppressant effect of methylphenidate was not subject to tolerance or sensitization. Methylphenidate blocked both the initiation to play and the responsivity to play initiation. The effect of methylphenidate was mimicked by the noradrenaline reuptake inhibitor atomoxetine, which is also used for the treatment of ADHD, and was blocked by an a-2 adrenoceptor antagonist. In addition, combined administration of subeffective doses of methylphenidate and atomoxetine suppressed social play. However, blockade of a-1 adrenoceptors, b-adrenoceptors, or dopamine receptors did not alter the effect of methylphenidate. These data show that methylphenidate selectively blocks the most vigorous part of the behavioral repertoire of adolescent rats through a noradrenergic mechanism. We suggest that the effect of methylphenidate on social play is a reflection of its therapeutic effect in ADHD, that is, improved behavioral inhibition. However, given the importance of social play for development, these findings may also indicate an adverse side effect of methylphenidate.

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Section: Methylphenidate Suppresses Social Play Through A-2 Adrenocepmentioning

confidence: 99%

Methylphenidate Disrupts Social Play Behavior in Adolescent Rats

Vanderschuren

Trezza

Griffioen-Roose

et al. 2008

Neuropsychopharmacol

144

View full text Add to dashboard Cite

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“…Atomoxetine (tomoxetine, LY 139603) is a selective noradrenaline (NA) reuptake blocker (Bymaster et al, 2002;Swanson et al, 2006) used clinically to treat both adult and childhood attention deficit hyperactivity disorder (ADHD) (Kratochvil et al, 2003(Kratochvil et al, , 2006Wilens, 2006). Unlike other medications used in ADHD, such as amphetamine and methylphenidate, atomoxetine has no appreciable affinity for dopamine (DA) receptors or the DA transporter, although it may indirectly boost prefrontal cortical DA via its effects on the NA transporter (Bymaster et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Similar Effects of the Selective Noradrenaline Reuptake Inhibitor Atomoxetine on Three Distinct Forms of Impulsivity in the Rat

Robinson

Eagle

Mar

et al. 2007

Neuropsychopharmacol

324

285

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Atomoxetine is a noradrenaline-specific reuptake inhibitor used clinically for the treatment of childhood and adult attention deficit hyperactivity disorder (ADHD). Studies in human volunteers and patient groups have shown that atomoxetine improves stop-signal reaction time (SSRT) performance, an effect consistent with a reduction in motor impulsivity. However, ADHD is a heterogeneous disorder and it is of interest to determine whether atomoxetine is similarly effective against other forms of impulsivity, as well as the attentional impairment present in certain subtypes of ADHD. The present study examined the effects of atomoxetine on impulsivity using an analogous SSRT task in rats and two additional tests of impulsivity; delay discounting of reward and the five-choice serial reaction time task (5CSRTT), the latter providing an added assessment of sustained visual attention. Atomoxetine produced a significant dosedependent speeding of SSRT. In addition, atomoxetine produced a selective, dose-dependent decrease in premature responding on the 5CSRTT. Finally, on the delay-discounting task, atomoxetine significantly decreased impulsivity by increasing preference for the large-value reward across increasing delay. These findings conclusively demonstrate that atomoxetine decreases several distinct forms of impulsivity in rats. The apparent contrast of these effects with stimulant drugs such as amphetamine and methylphenidate, which generally act to increase impulsivity on the 5CSRTT, may provide new insights into the mechanisms of action of stimulant and nonstimulant drugs in ADHD.

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“…Findling: What other issues do you raise when educating the families? Dr. Greenhill: I share the evidence that suggests that stimulants 31 and atomoxetine 32 are associated with a reduction in growth rates. For example, some children show a lower rate of height and weight gain.…”

Section: Stimulant Effects On Children's Growthmentioning

confidence: 98%