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Atomoxetine

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Atomoxetine is a biochemical compound designed for use in laboratory settings. It is a synthetic molecule with a specific chemical structure and properties, intended for research and scientific applications. The core function of Atomoxetine is to serve as a tool for researchers and scientists in their investigations, without making claims about its intended use or applications.

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7 protocols using atomoxetine

1

Dose-dependent Effects of Psychostimulants and Norepinephrine Modulator

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Doses of each drug were administered according to a Latin square design (8 sequences, counterbalanced) with one day of washout (no behavior) and one day of baseline performance between each dose, and one week of baseline sessions between each drug. All drugs were prepared fresh daily, dissolved in 0.9% sterile saline and administered at a volume of 1 mL/kg, i.p. The assessed drugs were amphetamine (0.0, 0.3, 0.6 and 1.0 mg/kg doses, 10 min prior to testing, sourced from Sigma; (54 (link))), atomoxetine (0.0, 0.1, 0.3 and 1.0 mg/kg doses, 15 min prior to testing, sourced from Tocris; (55 (link))), and amantadine (0, 10, 20, 40 mg/kg doses, 15 min prior to testing, sourced from Sigma, dosing based on (35 )).
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2

Selective Neuromodulator Effects on Mouse Behavior

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In all experiments mice were administered the selective COMT inhibitor tolcapone (30mg/kg; TRC Inc)(25 (link),41 (link)) and/or the selective DAT blocker GBR-12909 dihydrochloride (6mg/kg, Tocris)(42 (link)). These doses are effective at altering behavior without causing motor stereotypies (see Supplementary Information). D-amphetamine (in sulfate formulation; Tocris) was used at 4mg/kg (43 (link)), and the NET blocker atomoxetine (in hydrochloride formulation; Tocris) at 1mg/kg (44 (link)) in the voltammetry experiment only. All drugs were dissolved in 20% hydroxypropyl-beta-cyclodextrin (Acros Organics) in 0.9% saline (AquPharm), which served as a vehicle control in all experiments. All drugs were delivered by intraperitoneal injection.
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3

Selective Neuromodulator Effects on Mouse Behavior

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In all experiments mice were administered the selective COMT inhibitor tolcapone (30mg/kg; TRC Inc)(25 (link),41 (link)) and/or the selective DAT blocker GBR-12909 dihydrochloride (6mg/kg, Tocris)(42 (link)). These doses are effective at altering behavior without causing motor stereotypies (see Supplementary Information). D-amphetamine (in sulfate formulation; Tocris) was used at 4mg/kg (43 (link)), and the NET blocker atomoxetine (in hydrochloride formulation; Tocris) at 1mg/kg (44 (link)) in the voltammetry experiment only. All drugs were dissolved in 20% hydroxypropyl-beta-cyclodextrin (Acros Organics) in 0.9% saline (AquPharm), which served as a vehicle control in all experiments. All drugs were delivered by intraperitoneal injection.
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4

Enhancing Reversal Learning via Norepinephrine

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Electrical stimulation of the vagus nerve activates the LC and stimulates forebrain norepinephrine release (Groves, Bowman, & Brown, 2005 (link); Hulsey et al., 2017 (link); Roosevelt et al., 2006 (link); Shen et al., 2012 (link)). To determine whether an increase in norepinephrine availability could contribute to the enhancing effects of VNS on reversal learning, rats (n = 10) received intraperitoneal injections (1.0 ml/kg) of the norepinephrine reuptake inhibitor atomoxetine (Tocris Bioscience, 1.0 mg/kg) or vehicle (50:50 dimethyl sulfoxide in 0.9% saline) 15 min prior to the start of reversal learning sessions. This dose of atomoxetine was chosen based on previous work demonstrating its efficacy in enhancing multiple forms of cognitive flexibility in rats (Seu et al., 2009 (link); Totah, Logothetis, & Eschenko, 2015 (link)). The experimental design was otherwise identical to that of Experiment 1.
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5

Atomoxetine Effects on Extinction Recall

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The following day, 45 min before the training session rats were injected with atomoxetine (1.0 mg kg−1 intraperitoneal (i.p.), Tocris, Ellisville, MO, USA; dissolved in saline and administered in a volume of 1 ml kg−1) or an equivalent volume of saline. This dose was chosen on the basis of previous studies that found this dose to be effective in reducing spontaneous recovery of responding for food or cocaine.14 (link), 20 (link) Rats then underwent a 10-min extinction session in the extinction context.
Tests. One week later, rats underwent two tests across 2 days, one in the acquisition and one in the extinction contexts in a counterbalanced order. The tests were the same as the initial extinction sessions; the levers were introduced and response was recorded for 10 min.
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6

Atomoxetine Effects on Rat Behavior

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A single cohort of rats (n = 11) was used to test the effects of Atomoxetine (selective norepinephrine reuptake inhibitor). Atomoxetine (Tocris Bioscience) was prepared in 50:50 DMSO and 0.9% saline and administered i.p. (Baarendse et al. 2013 (link)).
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7

Neuroblastoma and Glioblastoma Cell Culture

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Human neuroblastoma cell line SH-SY5Y and human glioblastoma cell line U-87 MG were purchased from the American Type Culture Collection (Rockville, MD, USA). Cells were maintained in Dulbecco’s Modified Eagle’s Medium (Welgene; Seoul, Korea) supplemented with 10% fetal bovine serum (Welgene), 100 U/mL penicillin, and 0.1 mg/mL streptomycin (Welgene) in 95% air and 5% CO2 at 37°C. Cells were seeded at a density of 2×106/mL in 6-well plates or 150 mm dishes. The next day, cell media was changed to serum-free media and cells were treated with different concentration of atomoxetine hydrochloride or fluoxetine hydrochloride (Sigma-Aldrich; St. Louis, MO, USA) dissolved in dimethyl sulfoxide (DMSO). STO-609, a CaMKKα and CaMKKβ inhibitor [26 (link)], was purchased from Tocris (Ellisville, MO, USA) was prepared in DMSO and 2.5 μg/mL concentration administered 30 min before atomoxetine and fluoxetine treatments.
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