Selective Norepinephrine Reuptake Inhibition by Atomoxetine Prevents Cue-Induced Heroin and Cocaine Seeking

Abstract

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). 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. 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. Selective norepinephrine transporter inhibition by ATO might be an effective treatment for the prevention of relapse to both stimulant and opiate addiction.