Repeated lofexidine treatment attenuates stress-induced, but not drug cues-induced reinstatement of a heroin-cocaine mixture (speedball) seeking in rats
D. Highfield et al., Repeated lofexidine treatment attenuates stress-induced, but not drug cues-induced reinstatement of a heroin-cocaine mixture (speedball) seeking in rats, NEUROPSYCH, 25(3), 2001, pp. 320-331
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.