Conditioned Narcotic Withdrawal in Humans

O’Brien, Charles P.; Testa, Thomas J.; O'Brien, Thomas J; Brady, John Paul; Wells, Barbara G.

doi:10.1126/science.841320

Cited by 200 publications

(97 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, conditioning to a drug of abuse renders the conditioning context prone to a withdrawal response that is context-specific. Our results agree with the hypothesis proposed by several authors (25,(36)(37)(38)(39) that opiate withdrawal symptoms frequently reflect classically conditioned responses. Evidence of context-specific withdrawal exists in both humans and animals, and this conditioned withdrawal is believed to be an important factor that precipitates craving and relapse in abstinent ex-addicts (1,37,40).…”

Section: Discussionsupporting

confidence: 83%

Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner

Taubenfeld¹,

Muravieva²,

García‐Osta³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts.addiction | reconsolidation | hippocampus morphine

show abstract

Section: Discussionsupporting

confidence: 83%

Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner

Taubenfeld¹,

Muravieva²,

García‐Osta³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The presentation of drug-associated stimuli promotes drug seeking and relapse in addicts (Ehrman et al, 1992;Foltin and Haney, 2000;Heather et al, 1991;O'Brien et al, 1990;O'Brien et al, 1977). Thus, pharmacological manipulations that disrupt retrieval of long-term memories offer a particularly efficacious avenue for therapies targeting the elimination of these drug-associated memories.…”

Section: Time In Chamber (Sec)mentioning

confidence: 99%

“…Presentation of these cues can elicit craving in humans (Childress et al, 1986;Ehrman et al, 1992;Foltin and Haney, 2000;O'Brien et al, 1977) and stimulate active drug seeking in rodents (Banna et al, 2010;Chauvet et al, 2009;Fuchs et al, 2004;Mueller and Stewart, 2000). The associations between these cues and the drug reinforcer are acquired, consolidated, and readily retrieved in the presence of the cues.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of β-Adrenergic Receptors Induces a Persistent Deficit in Retrieval of a Cocaine-Associated Memory Providing Protection against Reinstatement

Otis

Mueller

2011

Neuropsychopharmacol

View full text Add to dashboard Cite

Drug-seeking behavior is maintained by encounters with drug-associated cues. Preventing retrieval of drug-associated memories that these cues provoke would therefore limit relapse susceptibility; however, little is known regarding the mechanisms of retrieval. Here, we show that b-adrenergic receptor activation is necessary for the retrieval of a cocaine-associated memory. Using a conditioned place preference (CPP) procedure, rats were conditioned to associate one chamber, but not another, with cocaine. When administered before a CPP trial, propranolol, but not saline, prevented retrieval of a cocaine-associated CPP. In subsequent drug-free trials, rats previously treated with propranolol continued to show a retrieval deficit, as no CPP was evident. This retrieval deficit was long lasting and robust, as the CPP did not re-emerge during a test for spontaneous recovery 14 days later or reinstate following a priming injection of cocaine. Moreover, the peripheral b-adrenergic receptor antagonist sotalol did not affect retrieval. Thus, retrieval of cocaine-associated memories is mediated by norepinephrine acting at central b-adrenergic receptors. Our findings support the use of propranolol, a commonly prescribed b-blocker, as an adjunct to exposure therapy for the treatment of addiction by preventing retrieval of drugassociated memories during and long after treatment, and by providing protection against relapse.

show abstract

“…Animal models showed that environmental cues associated with drug availability could provoke conditioned withdrawal symptoms and reinstatement of drug taking (Goldberg and Schuster, 1970). The Penn/VA human laboratory showed in human beings, for the first time, that opiate withdrawal symptoms (tearing of the eyes, runny nose, tachycardia, nausea, vomiting) and subjective craving for heroin could be produced as a conditioned response in the laboratory (O'Brien et al, 1977). One of the papers demonstrating this phenomenon was published in Science and consisted of training trials in which an odor was paired with a small dose of naloxone given to methadone-maintained volunteers.…”

Section: Addiction Is a Chronic Disease Of The Brainmentioning

confidence: 99%