Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure

Epstein, David H.; Preston, Kenzie L.; Stewart, Jane; Shaham, Yavin

doi:10.1007/s00213-006-0529-6

Cited by 585 publications

(505 citation statements)

References 195 publications

(182 reference statements)

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“…The role of the kappa opioid receptor in stress-and cocaine-priming-induced reinstatement Stress exposure has been found to potentiate addictive drug related behaviors (for example Covington and Miczek 2005;McLaughlin et al 2003McLaughlin et al , 2006a, and stress is a major precipitating factor for relapse of drug seeking (Epstein et al 2006;Stewart 2003). The principal findings of the present study were that reinstatement of cocaine seeking by stress exposure, but not by cocaine priming, was kappa-opioid-receptor-mediated.…”

Section: Discussionmentioning

confidence: 49%

“…Towards this goal, animal models of relapse were developed that identified triggers for reinstatement of drug selfadministration Stewart 1981, 1983;Gerber and Stretch 1975;Stretch and Gerber 1973). Drug reinstatement studies have shown that presentation of drug-associated cues, drug priming, and acute footshock stress each increased drug self-administration (see Bossert et al 2005;Epstein et al 2006;Shaham et al 2003). While the direct extension from animal models of reinstatement to human addiction experience may be problematic (Katz and Higgins 2003), a relationship between stress and drug addiction has been repeatedly noted (see Koob 2006), and treatments that enhance stress resilience might reduce the frequency of relapse.…”

Section: Introductionmentioning

confidence: 99%

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Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system

2008

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Introduction-Prior activation of the kappa opioid system by repeated stress or agonist administration has been previously shown to potentiate the rewarding properties of subsequently administered cocaine. In the present study, intermittent and uncontrollable footshock, a single session of forced swim, or acute administration of the kappa agonist U50,488 (5 mg/kg) were found to reinstate place preference in mice previously conditioned with cocaine (15 mg/kg) and subsequently extinguished by repeated training sessions without drug.

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Section: Discussionmentioning

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system

2008

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“…For example, sign-tracking CR performance of alcohol drinking in rats is virtually unchanged following a 27-day retention interval (Tomie et al, 2002c) or following a 41-day retention interval (Tomie et al, 2004a). Maintenance of sign-tracking CR performance of sipper CSdirected alcohol drinking over time, without appreciable decay or deterioration in the performance, is similar to relapse in humans and reinstatement of drug-taking in animals (Kruzich et al, 2001;Stewart, 2004; for review of reinstatement as a model of relapse, see Epstein et al, 2006;Fattore et al, 2007). In each of these cases there is little evidence of loss of responding during the retention interval, even though responding is not practiced during this extended period of time.…”

Section: Relapse-like Effectsmentioning

confidence: 99%

Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse

Tomie

Grimes

Pohorecky

2008

Brain Research Reviews

153

134

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Drug abuse researchers have noted striking similarities between behaviors elicited by Pavlovian signtracking procedures and prominent symptoms of drug abuse. In Pavlovian sign-tracking procedures, repeated paired presentations of a small object (conditioned stimulus, CS) with a reward (unconditioned stimulus, US) elicits a conditioned response (CR) that typically consists of approaching the CS, contacting the CS, and expressing consummatory responses at the CS. Signtracking CR performance is poorly controlled and exhibits spontaneous recovery and long-term retention, effects that resemble relapse. Sign-tracking resembles psychomotor activation, a syndrome of behavioral responses evoked by addictive drugs, and the effects of sign-tracking on corticosterone levels and activation of dopamine pathways resemble the neurobiological effects of abused drugs. Finally, the neurobiological profile of individuals susceptible to sign-tracking resembles the pathophysiological profile of vulnerability to drug abuse, and vulnerability to sign-tracking predicts vulnerability to impulsive responding and alcohol self-administration. Implications of sign-tracking for models of drug addiction are considered.

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“…In this study, we used a rat model of relapse to heroin seeking (Epstein et al, 2006), in which animals selfadminister heroin in the presence of compound cues (Van den Oever et al, 2008). We show that heroin selfadministration leads to long-term changes in synaptic levels of ECM constituents in the mPFC.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Matrix Plasticity and GABAergic Inhibition of Prefrontal Cortex Pyramidal Cells Facilitates Relapse to Heroin Seeking

Oever

Lubbers

Goriounova

et al. 2010

Neuropsychopharmacol

113

106

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Successful treatment of drug addiction is hampered by high relapse rates during periods of abstinence. Neuroadaptation in the medial prefrontal cortex (mPFC) is thought to have a crucial role in vulnerability to relapse to drug seeking, but the molecular and cellular mechanisms remain largely unknown. To identify protein changes that contribute to relapse susceptibility, we investigated synaptic membrane fractions from the mPFC of rats that underwent 21 days of forced abstinence following heroin self-administration. Quantitative proteomics revealed that long-term abstinence from heroin self-administration was associated with reduced levels of extracellular matrix (ECM) proteins. After extinction of heroin self-administration, downregulation of ECM proteins was also present in the mPFC, as well as nucleus accumbens (NAc), and these adaptations were partially restored following cue-induced reinstatement of heroin seeking. In the mPFC, these ECM proteins are condensed in the perineuronal nets that exclusively surround GABAergic interneurons, indicating that ECM adaptation might alter the activity of GABAergic interneurons. In support of this, we observed an increase in the inhibitory GABAergic synaptic inputs received by the mPFC pyramidal cells after the re-exposure to heroin-conditioned cues. Recovering levels of ECM constituents by metalloproteinase inhibitor treatment i.c.v.) prior to a reinstatement test attenuated subsequent heroin seeking, suggesting that the reduced synaptic ECM levels during heroin abstinence enhanced sensitivity to respond to heroin-conditioned cues. We provide evidence for a novel neuroadaptive mechanism, in which heroin self-administrationinduced adaptation of the ECM increased relapse vulnerability, potentially by augmenting the responsivity of mPFC GABAergic interneurons to heroin-associated stimuli.

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Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure

Cited by 585 publications

References 195 publications

Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system

Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system

Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse

Extracellular Matrix Plasticity and GABAergic Inhibition of Prefrontal Cortex Pyramidal Cells Facilitates Relapse to Heroin Seeking

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