Archival ReportSelective Norepinephrine Reuptake Inhibition by Atomoxetine Prevents Cue-Induced Heroin and Cocaine Seeking
Section snippets
Animals
Outbred male Lister Hooded rats (Charles River, Margate, United Kingdom) weighing 300–330 g at the beginning of the experiments were used. Rats were housed individually, under temperature- and humidity-controlled conditions and a reversed 12-hour light/dark cycle (lights off at 7:00 am). Water was available ad libitum, and food was given at the end of each day's testing. All experimental procedures conformed to the UK (1986) Animal (Scientific Procedures) Act (Project license 80/2234).
Drugs
Cocaine
All animals (n = 12) acquired responding for cocaine under a second-order schedule, making on average nearly 300 responses in 15 min for the first cocaine infusion. As expected, responding increased during the second interval, because of the self-administration of cocaine (14). During the course of the experiment, catheter patency was lost in one animal, which was therefore excluded from the analysis. Treatment with ATO resulted in a significant dose-dependent decrease in the number of active
Discussion
The results of this study show that selective NE reuptake inhibition by ATO had the remarkable effect of greatly reducing both cocaine and heroin seeking as well as diminishing the propensity to relapse to cocaine seeking. By contrast, MPH had no effect on either cocaine or heroin seeking and, as with ATO, at doses known to affect impulsivity (21). The effects of ATO were especially seen under the second-order schedule of reinforcement, in which seeking responses are maintained with vigor over
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2017, Pharmacology Biochemistry and BehaviorCitation Excerpt :What has not been addressed is whether atomoxetine will function as a cognitive enhancer in abstinent individuals with CUD who do not have ongoing cocaine use. This remains an important clinical consideration given the suggestions from pre-clinical research that atomoxetine may show promise as a relapse prevention aid (Brenhouse et al., 2010; Broos et al., 2015; Economidou et al., 2011; Jordan et al., 2014; Zlebnik and Carroll, 2015) and human laboratory studies suggesting that atomoxetine may diminish the acute effects of cocaine (Cantilena et al., 2012; Stoops et al., 2008) or d-amphetamine (Sofuoglu et al., 2009). Associations between poorer cognitive function and worse treatment engagement or substance use outcomes during or following treatment (Carroll et al., 2011; Kiluk et al., 2011; Streeter et al., 2008; Teichner et al., 2001), including likelihood of relapse (Fox et al., 2009), underline the theoretical potential for cognitive improvements to improve substance use outcomes or enhance the efficacy of cognitively demanding behavioral treatments like cognitive behavioral therapy.