Nicotine is a major addictive drug that recruits the endogenous opioid system for some of its addictive effects. We have validated sophisticated behavioral models for the evaluation of genetic factors that contribute to nicotine addiction in mice. These models will be used in conventional and tissue-specific opioid receptor and opioid peptide knockout mice to dissect the participation of opioid mechanisms in nicotine addiction and to identify genes related to nicotine consumption downstream of the opioid system.
The specific aims will be:
Specific Aim 1. To evaluate the involvement of opioid receptors and endogenous opioid peptides in the different components of nicotine addiction.
Specific Aim 2. To validate the behavioral changes observed in Aim 1 and clarify neural sites involved by using conditional tissue-specific knockout of opioid receptor and peptide genes.
Specific Aim 3. To identify genes regulated by nicotine downstream the opioid system. The potential impact of results obtained in this research project is of importance since nicotine addiction constitutes a major problem of public health in the world. These results will help to identify potential targets for the development of novel therapeutic strategies against nicotine addiction. Therefore, this project could provide a major progress in the management of nicotine dependence, and could have repercussions to improve the quality of live in the societies widely affected by the health and social-economic problems associated with nicotine addiction. Finally, the results and experimental strategies of this project would be also of interest for the study of other addictive processes, considering that the opioid system represents a common substrate to the addictive properties of most drugs of abuse.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Volman, Susan
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Pompeu Fabra University
Zip Code
Lutz, P E; Reiss, D; Ouagazzal, A M et al. (2013) A history of chronic morphine exposure during adolescence increases despair-like behaviour and strain-dependently promotes sociability in abstinent adult mice. Behav Brain Res 243:44-52
Le Merrer, Julie; Faget, Lauren; Matifas, Audrey et al. (2012) Cues predicting drug or food reward restore morphine-induced place conditioning in mice lacking delta opioid receptors. Psychopharmacology (Berl) 223:99-106
Bilkei-Gorzo, Andras; Erk, Susanne; Schurmann, Britta et al. (2012) Dynorphins regulate fear memory: from mice to men. J Neurosci 32:9335-43
Le Merrer, Julie; Befort, Katia; Gardon, Olivier et al. (2012) Protracted abstinence from distinct drugs of abuse shows regulation of a common gene network. Addict Biol 17:1-12
Del Boca, C; Lutz, P E; Le Merrer, J et al. (2012) Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and antidepressant-like effects in mice. Neuroscience 218:185-95
Darcq, Emmanuel; Befort, Katia; Koebel, Pascale et al. (2012) RSK2 signaling in medial habenula contributes to acute morphine analgesia. Neuropsychopharmacology 37:1288-96
Darcq, Emmanuel; Koebel, Pascale; Del Boca, Carolina et al. (2011) RSK2 signaling in brain habenula contributes to place aversion learning. Learn Mem 18:574-8
Lutz, Pierre-Eric; Pradhan, Amynah A; Goeldner, Celia et al. (2011) Sequential and opposing alterations of 5-HT(1A) receptor function during withdrawal from chronic morphine. Eur Neuropsychopharmacol 21:835-40
Goeldner, Celia; Lutz, Pierre-Eric; Darcq, Emmanuel et al. (2011) Impaired emotional-like behavior and serotonergic function during protracted abstinence from chronic morphine. Biol Psychiatry 69:236-44
Le Merrer, Julie; Plaza-Zabala, Ainhoa; Del Boca, Carolina et al. (2011) Deletion of the ? opioid receptor gene impairs place conditioning but preserves morphine reinforcement. Biol Psychiatry 69:700-3

Showing the most recent 10 out of 50 publications