Drug and Alcohol Dependence 108 (2010) 183–194 Contents lists available at ScienceDirect Drug and Alcohol Dependence journal homepage: www.elsevier.com/locate/drugalcdep Review The endogenous opioid system: A common substrate in drug addiction José Manuel Trigo a , Elena Martin-García a , Fernando Berrendero a , Patricia Robledo a,b , Rafael Maldonado a,∗ a Laboratori de Neurofarmacologia, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, Barcelona, Spain b Institut Municipal d’Investigació Mèdica (IMIM), PRBB, Barcelona, Spain article info Article history: Received 23 June 2009 Received in revised form 30 September 2009 Accepted 28 October 2009 Available online 28 November 2009 Keywords: Reward Dependence Psychostimulants Nicotine Alcohol Cannabinoids abstract Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits that involve several neurotransmitters. One of the neurochemical systems that plays a pivotal role in different aspects of addiction is the endogenous opioid system (EOS). Opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within these reward circuits. Chronic exposure to the different prototypical drugs of abuse, including opioids, alcohol, nicotine, psychostimulants and cannabinoids has been reported to produce significant alterations within the EOS, which seem to play an important role in the development of the addictive process. In this review, we will describe the adaptive changes produced by different drugs of abuse on the EOS, and the current knowledge about the contribution of each component of this neurobiological system to their addictive properties. © 2009 Elsevier Ireland Ltd. All rights reserved. Contents 1. Introduction .......................................................................................................................................... 183 2. Mesolimbic system and addiction theories .......................................................................................................... 184 3. The endogenous opioid system ...................................................................................................................... 184 4. Endogenous opioid system in opioid addiction ..................................................................................................... 185 5. Endogenous opioid system in alcohol addiction .................................................................................................... 186 6. Endogenous opioid system in nicotine addiction ................................................................................................... 187 7. Endogenous opioid system in addiction to psychostimulants ...................................................................................... 187 8. Endogenous opioid system in cannabinoid addiction ............................................................................................... 189 9. Concluding remarks .................................................................................................................................. 189 Role of funding source ............................................................................................................................... 189 Conflict of interest ................................................................................................................................... 189 Contributors ......................................................................................................................................... 190 Acknowledgements .................................................................................................................................. 190 References ........................................................................................................................................... 190 Abbreviations: EOS, endogenous opioid systems; DA, dopamine; Nacc, nucleus accumbens; DAT, dopamine transporter; PFC, prefrontal cortex; CNS, central nervous system; POMC, proopiomelanocortin; PENK, proenkephalin; PDYN, pro- dynorphin; VTA, ventral tegmental area; CPP, conditioned place preference; THC, 9-tetrahydrocannabinol. ∗ Corresponding author at: Universitat Pompeu Fabra, Calle Dr. Aiguader, 88, 08003 Barcelona, Spain. Tel.: +34 933160824; fax: +34 933160901. E-mail address: rafael.maldonado@upf.edu (R. Maldonado). 1. Introduction Drug addiction is a chronic brain disorder characterized by the compulsive use of drugs in spite of their adverse consequences, loss of control over drug taking and relapse even after long peri- ods of drug abstinence. Drug addiction can be viewed as the result of a series of transitions from voluntary use in search of a hedonic experience, to loss of control over this behavior, and ultimately to habitual and compulsive behavior (see Everitt et al., 2008 for review). There are various risk factors that deter- 0376-8716/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.drugalcdep.2009.10.011