Effects of naltrexone on cocaine- and sucrose-seeking behaviour in response to associated stimuli in rats

Abstract

The non-selective opioid receptor antagonist naltrexone reduces cocaine-induced reinstatement of drugseeking behaviour in abstinent rats. The current study sought to determine whether the opioid system is also involved in cocaine-seeking behaviour induced by cocaine-associated stimuli in abstinent rats. Adult male rats were trained to press a lever either to self-administer cocaine or to obtain sucrose pellets in the presence of distinctive discriminative and conditioned stimuli. After a period of extinction, re-exposure to cocaine-associated cues selectively elicited robust and enduring responding at the active lever; sucrose pellet-associated cues revived seeking behaviour less pronouncedly. Pretreatment with naltrexone (0.25, 1, 2.5 mg/kg s.c., 20 min before reinstatement tests) dose dependently prevented cue-induced cocaineseeking behaviour, whereas (2.5 mg/kg s.c.) did not affect the degree of cue-induced sucrose-seeking behaviour. These results provide the first evidence that naltrexone influences cocaine seeking induced by conditioned stimuli in abstinent rats; this effect appears selective for cocaine reinstatement as opposed to a non-drug reinforcer.

Naloxone attenuates incubated sucrose craving in rats

“…The processing of these different types of cues appears to require different neural substrates (Phillips and LeDoux 1992;Holland and Bouton 1999). Second, we observed the most reliable effects of naloxone at day 30 of forced abstinence while Burattini et al (2007) tested responding after about 15 days of extinction. There is also the consideration of differences in efficacy to explain the discrepancy between naloxone and naltrexone; however, this is unlikely as the naltrexone dose (2.5 mg/kg) was similar to our higher doses.…”

“…In effect, the animal model is validated. However, a recent study of the effect of a single dose of naltrexone on responding in the presence of a discriminative stimulus, previously indicating the availability of sucrose, did not find any effect of naltrexone on conditioned responding (Burattini et al 2007). This inconsistency is likely due to several methodological issues.…”

“…This inconsistency is likely due to several methodological issues. First, we are studying relapse due to contingent presentation of a discrete cue formerly paired with sucrose, while Burattini et al (2007) evaluated the effects of a discriminative stimulus. The processing of these different types of cues appears to require different neural substrates (Phillips and LeDoux 1992;Holland and Bouton 1999).…”

“…They also decrease craving for cigarettes and alcohol (Epstein and King 2004;O'Malley et al 2002). In studies with rats, naltrexone decreases responding for cocaine cues (Burattini et al 2007), alcohol following alcohol cue exposure (Pickering and Liljequist 2003), and responding in the presence of an alcohol-paired discriminative stimulus (Ciccocioppo et al 2002). In addition, in cocaine-trained rats, Lu and Dempsey (2004) found that heroin had greater effects later in abstinence vs early on reinstating cocaine seeking behavior-a cross-sensitivity suggesting that either the DA or opiate system (or both) is altered over the incubation of craving.…”

Effects of Genetic Deletion of Endogenous Opioid System Components on the Reinstatement of Cocaine-Seeking Behavior in Mice

“…In agreement, pharmacological studies have shown that MOR antagonists reduced cocaine relapse in rats (Tang et al, 2005). Furthermore, the non-selective opioid antagonist naltrexone reduced cue-induced cocaine-seeking behavior (Burattini et al, 2008), and had no effects on cocaine priming-induced reinstatement in rats (Comer et al, 1993), although repeated naltrexone treatment suppressed this priming-induced reinstatement . Accordingly, microinjection of selective MOR agonists into the nucleus accumbens reinstated cocaine-seeking behavior in rats (Simmons and Self, 2009).…”