期刊
BIOLOGICAL PSYCHIATRY
卷 69, 期 3, 页码 266-274出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2010.09.040
关键词
Addiction; atomoxetine; impulsivity; methylphenidate; relapse; second-order
资金
- UK Medical Research Council (MRC) [G9536855]
- Wellcome Trust
- Medical Research Council [G0001354, G1000183B, G0600196, G1002231, G0001354B] Funding Source: researchfish
- MRC [G0600196, G1002231] Funding Source: UKRI
Background: Preventing relapse to drug use is a major challenge for drug addiction treatment. We have recently shown that impulsivity predating drug-taking increases the susceptibility to relapse to cocaine seeking and that treatment with the anti-impulsivity drug atomoxetine (ATO), a selective norepinephrine re-uptake inhibitor (norepinephrine transporter), prevents relapse. Here, we investigated further the effects of ATO on cue-maintained heroin and cocaine seeking and relapse and compared these effects with those of the anti-impulsivity stimulant drug methylphenidate (MPH). Methods: Rats were trained to seek and self-administer cocaine or heroin under a second-order schedule of reinforcement. After acquisition of stable responding, groups of rats (n = 10-12) were treated, in a within-subject design, with either ATO or MPH (.3-3.0 mg/kg IP), and the effects on cocaine and heroin seeking were measured. The effects of ATO (.3-1.0 mg/kg) on cue-induced relapse to cocaine seeking after a 1-week period of abstinence were also studied. Results: Atomoxetine significantly decreased both cue-controlled cocaine and heroin seeking, whereas MPH had no significant effect. Atomoxetine also significantly attenuated cue-induced relapse to cocaine seeking after abstinence. The effects of ATO were selective for cue-controlled drug-seeking, because it did not affect responding in the absence of the drug-paired cue; nor did it alter responding for oral sucrose, except minimally at the highest dose, or locomotor activity. Conclusions: Selective norepinephrine transporter inhibition by ATO might be an effective treatment for the prevention of relapse to both stimulant and opiate addiction.
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