Repeated lofexidine treatment attenuates stress-induced, but not drug cues-induced reinstatement of a heroin-cocaine mixture (speedball) seeking in rats

Alpha-2 adrenoceptor agonists (lofexidine, clonidine) are used to alleviate short-term opioid withdrawal in humans. In rats, acute injections of these agents attenuate stress-induced reinstatement of heroin and cocaine seekin g at time points that are beyond the acute drug withdrawal phase. Here, we studied whether exposure to lofexidine would attenuate reinstatement of a h eroin-cocaine mixture (speedball) seeking induced by exposure to stress or to drug-associated cues. Rats were trained to lever press for speedball for 10 days, and the drug-reinforced behavior was then extinguished for 11 day s in the presence (Experiment 1) or the absence (Experiment 2) of the drug cues. Subsequently, rats were tested for reinstatement of drug seeking afte r exposure to intermittent footshock stress (5-15 min; Experiment 1) or the drug cues (Experiment 2). Starting on day 7 of training, rats received dai ly injections of saline or lofexidine (0.1 or 0.2 mg/kg). Repeated lofexidi ne treatment significantly attenuated footshock-induced reinstatement, but did not alter drug cues-induced reinstatement of speedball seeking. fit add ition, lofexidine did not have a consistent effect on speedball self-admini stration and extinction behavior. Results extend previous reports with acut e drug injections, indicating that lofexidine maintains its effect on stres s-induced reinstatement after repeated treatment. The present data also sug gest that the neurochemical events underlying stress- and drug cues-induced relapse are not identical. (C) 2001 American College of Neuropsychopharmac ology. Published by Elsevier Science Inc.