Atomoxetine Increases Extracellular Levels of Norepinephrine and Dopamine in Prefrontal Cortex of Rat A Potential Mechanism for Efficacy in Attention Deficit/Hyperactivity Disorder

Bymaster, Frank P.; Katner, Jason; Nelson, David L.; Hemrick‐Luecke, Susan K.; Threlkeld, Penny G.; Heiligenstein, John H.; Morin, Stéphanie; Gehlert, Donald R.; Perry, Kenneth W.

doi:10.1016/s0893-133x(02)00346-9

Cited by 1,007 publications

(850 citation statements)

References 80 publications

Supporting

Mentioning

800

Contrasting

Unclassified

Order By: Relevance

“…2). It should, however, be noted that atomoxetine does influence DA release in the rat prefrontal cortex (Bymaster et al 2002), pinpointing the need for further studies in this area.…”

Section: Action Cancellationmentioning

confidence: 99%

The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks

2008

View full text Add to dashboard Cite

Background and rationale The term 'action inhibition' encapsulates the ability to prevent any form of planned physical response. Growing evidence suggests that different 'stages' or even subtypes of action inhibition activate subtly different neuropharmacological and neuroanatomical processes. Objectives In this review, we present evidence from two commonly used and apparently similar behavioural tests, the stop-signal task and the go/no-go task, to determine if these have similar neuroanatomical and neurochemical modulation. Results Whilst performance of the stop-signal and go/no-go tasks is modulated across only subtly different anatomical networks, serotonin (5-HT) is strongly implicated in inhibitory control on the go/no-go but not the stop-signal task, whereas the stop-signal reaction time appears more sensitive to the action of noradrenaline. Conclusions There is clear neuropharmacological and neuroanatomical evidence that stop-signal and go/no-go tasks represent different forms of action inhibition. This evidence translates with remarkable consistency across species. We discuss the possible implications of this evidence with respect to the development of novel therapeutic treatments for disorders in which inhibitory deficits are prominent and debilitating.

show abstract

“…2). It should, however, be noted that atomoxetine does influence DA release in the rat prefrontal cortex (Bymaster et al 2002), pinpointing the need for further studies in this area.…”

Section: Action Cancellationmentioning

confidence: 99%

The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks

2008

View full text Add to dashboard Cite

show abstract

“…Stimulants like methylphenidate (MPH) act as indirect dopamine (DA) agonists, inhibiting DA reuptake via occupation of the DA transporter (Volkow et al, 1998). MPH increases DA in striatum, and both norepinephrine (NE) and DA in prefrontal cortex (Bymaster et al, 2002). Atomoxetine (ATX), a nonstimulant, selective NE reuptake inhibitor (Zerbe et al, 1985) recently approved in the United States for treatment of ADHD, does not increase DA in striatum but, like MPH, increases both NE and DA in prefrontal cortex (Bymaster et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Inhibitory and Excitatory Effects of ADHD Medications Methylphenidate and Atomoxetine on Motor Cortex

Gilbert

Ridel

Sallee

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Stimulant and norepinephrine (NE) reuptake inhibitor medications have different effects at the neuronal level, but both reduce symptoms of attention deficit hyperactivity disorder (ADHD). To understand their common physiologic effects and thereby gain insight into the neurobiology of ADHD treatment, we compared the effects of the stimulant methylphenidate (MPH) and NE uptake inhibitor atomoxetine (ATX) on inhibitory and excitatory processes in human cortex. Nine healthy, right-handed adults were given a single, oral dose of 30 mg MPH and 60 mg ATX at visits separated by 1 week in a randomized, double-blind crossover trial. We used paired and single transcranial magnetic stimulation (TMS) of motor cortex to measure conditioned and unconditioned motor-evoked potential amplitudes at inhibitory (3 ms) and facilitatory (10 ms) interstimulus intervals (ISI) before and after drug administration. Data were analyzed with repeated measures, mixed model regression. We also analyzed our findings and the published literature with meta-analysis software to estimate treatment effects of stimulants and NE reuptake inhibitors on these TMS measures. There were no significant pretreatment differences or effects of treatment order. Both agents produced a significant increase in facilitation and a decrease in inhibition. Effects of ATX and MPH did not differ significantly. Pooled estimates from published studies show similar results for stimulants and NE reuptake inhibitors. In conclusion, in healthy adults, both stimulant and nonstimulant medications for ADHD decrease cortical inhibition and increase cortical facilitation. Cortical inhibition, shown previously to be abnormal in ADHD, may play a key role producing behavioral pathology.

show abstract

“…Microdialysis studies have shown that systemic injection of NA reuptake inhibitors (NRI) raised extracellular NA in the PFC, hippocampus, and LC (Bymaster et al, 2002;Dazzi et al, 2001;L'Heureux et al, 1986;Mateo et al, 1998;Page and Lucki, 2002;Sacchetti et al, 1999Sacchetti et al, , 2001). However, their effect is limited by the concurrent activation of presynaptic a 2 -adrenoceptors.…”

Section: Introductionmentioning

confidence: 99%

Chronic Reboxetine Desensitizes Terminal but not Somatodendritic α2-Adrenoceptors Controlling Noradrenaline Release in the Rat Dorsal Hippocampus

Parini

Renoldi

Battaglia

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

The slow onset of antidepressant drugs' effects is thought to reflect the time required for the development of adaptive changes such as desensitization of presynaptic autoreceptors controlling the release of neurotransmitters. Using in vivo microdialysis in conscious rats, we studied the effect of a continuous infusion of the selective noradrenaline (NA) reuptake inhibitor reboxetine on extracellular concentrations of NA. Doses of 10 mg/kg/day reboxetine through subcutaneous osmotic pumps for 2 days increased extracellular NA by 272% in the dorsal hippocampus (DH) of rats. NA rose significantly more in rats given reboxetine for 7 (469%) and 14 (437%) days. Intraperitoneal injection of 30 mg/kg clonidine, an a 2 -adrenoceptor agonist, reduced the release of NA to 49% of basal levels in rats given vehicle or reboxetine for 2 days, but this effect was markedly less in rats given reboxetine for 7 and 14 days. Likewise, the effect of intrahippocampal infusion of clonidine (0.05 and 0.2 mM) on extracellular NA was significantly attenuated in rats given reboxetine for 7 and 14 days, whereas the injection of 0.6 nmol clonidine into the locus coeruleus caused similar reductions of extracellular NA in the DH and prefrontal cortex (PFC) of rats infused with vehicle (DH À64%; PFC À42%) and reboxetine (DH À45%; PFC À28%) for 14 days. The results indicate that chronic treatment markedly enhances the effect of reboxetine on extracellular NA in the DH and suggest that this effect may be due to the desensitization of hippocampal a 2 -adrenoceptors.

show abstract

Atomoxetine Increases Extracellular Levels of Norepinephrine and Dopamine in Prefrontal Cortex of Rat A Potential Mechanism for Efficacy in Attention Deficit/Hyperactivity Disorder

Abstract: The selective norepinephrine (NE)

Cited by 1,007 publications

References 80 publications

The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks

The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks

Comparison of the Inhibitory and Excitatory Effects of ADHD Medications Methylphenidate and Atomoxetine on Motor Cortex

Chronic Reboxetine Desensitizes Terminal but not Somatodendritic α2-Adrenoceptors Controlling Noradrenaline Release in the Rat Dorsal Hippocampus

Contact Info

Product

Resources

About