Conditioning factors in drug abuse: can they explain compulsion?

O’Brien, Charles P.; Childress, Anna Rose; Ehrman, Ronald N.; Robbins, Steven J.

doi:10.1177/026988119801200103

Cited by 624 publications

(483 citation statements)

References 44 publications

Supporting

Mentioning

466

Contrasting

Unclassified

Order By: Relevance

“…Two major factors triggering relapse behaviour are stress and environmental conditioning experiences (American Psychiatric Association 1994;O'Brien and McLellan 1996;O'Brien et al 1990O'Brien et al , 1998, which probably facilitate relapse to alcohol seeking via distinct brain mechanisms. For example, activation of the mesolimbic dopamine system via an opioid-dependent mechanism (or via direct alterations in dopamine transmission in the basolateral nucleus of amygdala) seems to mediate the effect of drug-associated cues (Liu and Wiess 2002;Ciccocioppo et al 2001), and extrahypothalamic CRF within the bed nucleus of the stria terminalis and median raphe nucleus is likely to mediate stress-induced reinstatement of drug-seeking behaviour Lê and Shaham 2002).…”

Section: Discussionmentioning

confidence: 99%

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

et al. 2008

View full text Add to dashboard Cite

Rationale A major clinical concern with the use of cannabinoid receptor 1 (CB1) direct agonists is that these compounds increase alcohol drinking and drug abuserelated behaviours. As an alternative approach, CB1-receptor-mediated activity can be facilitated by increasing anandamide levels with the use of hydrolase fatty acid amide hydrolase (FAAH) inhibitors. Objective Using the selective FAAH inhibitor URB597, we investigated whether activation of the endogenous cannabinoid tone increases alcohol abuse liability, as what happens with the CB1 receptor direct agonists.Materials and methods URB597 was tested on alcohol self-administration in Wistar rats and on homecage alcohol drinking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. In Wistar rats, URB597 effects on alcohol-induced anxiety and on stress-, yohimbineand cue-induced reinstatement of alcohol seeking were also evaluated. For comparison, the effect of the CB1 receptor antagonist rimonabant on ethanol self-administration was also tested. Results Under our experimental condition, intraperitoneal (IP) administration of URB597 (0.0, 0.3 and 1.0 mg/kg) neither increased voluntary homecage alcohol drinking in msP rats nor facilitated fixed ratio 1 and progressive ratio alcohol self-administration in nonselected Wistars. In the reinstatement tests, the compound did not have effects on cue-, footshock stress-and yohimbine-induced relapse. Conversely, URB597 completely abolished the anxiogenic response measured during withdrawal after an acute IP administration of alcohol (3.0 g/kg). Rimonabant (0.0, 0.3, 1.0 and 3.0 mg/kg) significantly reduced ethanol self-administration. Conclusions Results demonstrate that activation of the endocannabinoid anandamide system by selective inhibition of FAAH does not increase alcohol abuse risks but does reduce anxiety associated to alcohol withdrawal. We thus can speculate that medication based on the use of endocannabinoid system modulators such as URB597 may offer important advantages compared to treatment with direct CB1 receptor activators.

show abstract

Section: Discussionmentioning

confidence: 99%

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Finally, there may be additional benefits deriving from other actions of ACPC. While relapse to substance abuse is driven in part by conditioned responses to environmental stimuli (O'Brien et al 1998;Tiffany and Carter 1998), two of the major precipitants of relapse are dysphoric moods and the stress associated with interpersonal conflicts (Marlatt and George 1984). The profile of ACPC includes not only the ability to block the secondary reinforcing effects of stimuli associated with drug taking, but also, antidepressant and anxiolytic properties.…”

Section: Discussionmentioning

confidence: 99%

“…During the maintenance phase, a number of factors have been identified that predispose to relapse. These include stimuli associated with drug taking (O'Brien et al 1998). The place preference conditioning procedure has been used extensively as an animal model for investigating the rewarding properties of drug-conditioned stimuli.…”

mentioning

confidence: 99%

Selective Blockade of Drug-induced Place Preference Conditioning by ACPC, a Functional NDMA-receptor Antagonist

Papp

Gruca

Willner

2002

Neuropsychopharmacology

View full text Add to dashboard Cite

ACPC (1-aminocyclopropanecarboxylic acid) is a partial agonist at the strychnine-insensitive glycine receptor site on the NMDA receptor complex, and a functional NMDA antagonist. A series of experiments was conducted to assess the effects of ACPC in a biased place conditioning paradigm. As previously reported, ACPC itself did not support either appetitive or aversive place conditioning. However, co-administration of ACPC (200 mg/kg) blocked the acquisition of place preferences conditioned using a variety of psychoactive drugs (amphetamine, cocaine, nomifensine, diazepam, morphine, nicotine). No tolerance was seen to this effect following two weeks of chronic ACPC administration. Overall, ACPC did not affect the expression of place conditioning when administered immediately before the post-conditioning test. However, these effects appeared somewhat variable between drugs, and further analysis showed that ACPC did block the expression of preferences conditioned with some drugs (diazepam, morphine, nicotine), but not others (amphetamine, cocaine, nomifensine). The effects of ACPC could not be accounted for by state dependence, as ACPC blocked morphine and cocaine place preferences when administered during both the acquisition and the expression phase of conditioning. In contrast to the blockade by ACPC of drug-induced place preferences, ACPC had no effect on the acquisition of place preferences conditioned using a variety of natural non-drug reinforcers (food, sucrose, social interaction, novelty). ACPC also had no effect on the acquisition of drug-induced place aversions (naloxone, picrotoxin The treatment of drug addiction has two targets: cessation or reduction of use, and maintenance of those gains. During the maintenance phase, a number of factors have been identified that predispose to relapse. These include stimuli associated with drug taking (O'Brien et al. 1998). The place preference conditioning procedure has been used extensively as an animal model for investigating the rewarding properties of drug-conditioned stimuli. In this procedure, 27 , NO . 5 the animal experiences the effects of a drug while confined in a distinctive environment; subsequently the animal is offered a choice between the drug-paired environment and an environment that has been experienced in the drug-free state. Subject to certain methodological considerations, a preference for the drug-paired environment is interpreted to mean that the environment has acquired secondary reinforcing properties as a consequence of its pairing with a primary reinforcer. Drugs that support the development of a conditioned place preference (CPP) are generally those that are abused by people (e.g. psychostimulants, opioids, benzodiazepines, alcohol, nicotine), while drugs that do not support CPP are typically not abused (e.g. neuroleptics, antidepressants, antihistamines) (Carr et al. 1989;Schechter and Calcagnetti 1993;Calcagnetti and Schechter 1998;Tzschentke 1998). In addition to drug rewards, CPP can also be used to study the reinforcing prop...

show abstract

“…Relapse liabilityFthe likelihood that a cocaine-abstinent, formally cocaine-dependent individual will resume cocaine useFhas been shown to be associated with a number of factors. Stress, environmental cues, and conditioned stimuli have all been demonstrated clinically to play roles in cocaine relapse (Wallace, 1989;O'Brien et al, 1998;Sinha, 2001). For treatment of cocaine addiction, relapse prevention presents the most promising point for intervention (O'Brien, 2005).…”

Section: Introductionmentioning

confidence: 99%

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Freeman

Patel

Brucklacher

et al. 2007

Neuropsychopharmacol

110

126

View full text Add to dashboard Cite

Cocaine-responsive gene expression changes have been described after either no drug abstinence or short periods of abstinence. Little data exist on the persistence of these changes after long-term abstinence. Previously, we reported that after discrete-trial cocaine selfadministration and 10 days of forced abstinence, incubation of cocaine reinforcement was observable by a progressive ratio schedule. The present study used rat discrete-trial cocaine self-administration and long-term forced abstinence to examine extinction responding, mRNA abundance of known cocaine-responsive genes, and chromatin remodeling. At 30 and 100 days of abstinence, extinction responding increased compared to 3-day abstinent rats. Decreases in both medial prefrontal cortex (mPFC) and nucleus accumbens cfos, Nr4a1, Arc, and EGR1 mRNA were observed, and in most cases persisted, for 100 days of abstinence. The signaling peptides CART and neuropeptide Y (NPY) transiently increased in the mPFC, but returned to baseline levels following 10 days of abstinence. To investigate a potential regulatory mechanism for these persistent mRNA changes, levels of histone H3 acetylation at promoters for genes with altered mRNA expression were examined. In the mPFC, histone H3 acetylation decreased after 1 and 10 days of abstinence at the promoter for EGR1. H3 acetylation increased for NPY after 1 day of abstinence and returned to control levels by 10 days of abstinence.Behaviorally, these results demonstrate incubation after discrete-trial cocaine self-administration and prolonged forced abstinence. This incubation is accompanied by changes in gene expression that persist long after cessation of drug administration and may be regulated by chromatin remodeling.

show abstract

Conditioning factors in drug abuse: can they explain compulsion?

Cited by 624 publications

References 44 publications

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

Selective Blockade of Drug-induced Place Preference Conditioning by ACPC, a Functional NDMA-receptor Antagonist

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Contact Info

Product

Resources

About