Addiction involves a complex neuropharmacologic behavioural cycle, in which positive reinforcement exerted by the drug and the negative state of withdrawal drive the user to extremes to obtain the drug. Comprehensive studies have established that relapse is the most common outcome of recovery programs treating addictive behaviours. Several types of anticraving medication are available nowadays, such as naltrexone for the treatment of alcoholism, bupropion for nicotine, methadone or buprenorphine for heroin. This review focuses on recent behavioural data providing a rationale for an endocannabinoid mechanism underlying reinstatement of compulsive drug seeking. Studies supporting the contention that reinstatement of extinguished drug self-administration behaviour may be generated by cannabinoid CB I receptor agonists and attenuated, if not blocked. by CB I receptor antagonists, are here reviewed. In support to these findings, conditioned place preference studies substantiate the involvement of the endocannabinoid system in recidivism mechanisms by demonstrating that motivation to relapse can be triggered by CB I receptor activation while blockade of such receptors may prevent reinstatement of place conditioning induced by either drug primings or drug-associated cues. Finally biochemical studies evaluating changes in endocannabinoid levels, CB I receptor density and CB I mRNA expression during re-exposure to drug following extinction are also examined. Taken together, the evidence available has important implications in the understanding and treatment of relapsing episodes in patients undergoing detoxification.

Endocannabinoid regulation of relapse mechanisms

FADDA, PAOLA;FRATTA, WALTER
2007-01-01

Abstract

Addiction involves a complex neuropharmacologic behavioural cycle, in which positive reinforcement exerted by the drug and the negative state of withdrawal drive the user to extremes to obtain the drug. Comprehensive studies have established that relapse is the most common outcome of recovery programs treating addictive behaviours. Several types of anticraving medication are available nowadays, such as naltrexone for the treatment of alcoholism, bupropion for nicotine, methadone or buprenorphine for heroin. This review focuses on recent behavioural data providing a rationale for an endocannabinoid mechanism underlying reinstatement of compulsive drug seeking. Studies supporting the contention that reinstatement of extinguished drug self-administration behaviour may be generated by cannabinoid CB I receptor agonists and attenuated, if not blocked. by CB I receptor antagonists, are here reviewed. In support to these findings, conditioned place preference studies substantiate the involvement of the endocannabinoid system in recidivism mechanisms by demonstrating that motivation to relapse can be triggered by CB I receptor activation while blockade of such receptors may prevent reinstatement of place conditioning induced by either drug primings or drug-associated cues. Finally biochemical studies evaluating changes in endocannabinoid levels, CB I receptor density and CB I mRNA expression during re-exposure to drug following extinction are also examined. Taken together, the evidence available has important implications in the understanding and treatment of relapsing episodes in patients undergoing detoxification.
2007
CB1 RECEPTOR, REINSTATEMENT, SELF-ADMINISTRATION, CONDITIONED PLACE PREFERENCE, ADDICTION
File in questo prodotto:
File Dimensione Formato  
Fattore et al. - Pharmacol Res.pdf

Solo gestori archivio

Tipologia: versione pre-print
Dimensione 1.91 MB
Formato Adobe PDF
1.91 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/100587
Citazioni
  • ???jsp.display-item.citation.pmc??? 18
  • Scopus 46
  • ???jsp.display-item.citation.isi??? 39
social impact