Laboratory on the Neurobiology of Eating and Addictive Disorders

DR BENJAMIN BOUTREL, PD MER

Field of expertise

Our laboratory develops animal models for a better understanding of the neural circuits underlying for decision-making processes, particularly in the context of addictive disorders. Our goal is to identify the underpinnings of sensation seeking, risk taking, substance abuse and pathological gambling behaviors. We focus our investigations on the adolescent brain and we try to assess how episodes of stress or of excessive drug consumption impact the adult brain functioning.

For the past eight years, we have contributed to the identification of a novel peptidergic pathway involved in the modulation of the reinforcing properties of drugs of abuse, namely the hypocretin (also called orexin) system. We have completed our initial work (primarily focused on the pharmacology of this system) by studying the behavior of transgenic mice deficient in hypocretin/orexin, and we now use optogenetic technology to confirm our assumptions.

Grants and funding

  • Grant from the Swiss National Science Foundation (NCCR-1125759), 2010-2014 (co-recipient) : Endophenotyping of drug addiction (NCCR directed by Prof. Pierre Magistretti).
  • Grant from the Swiss National Science Foundation (3100A-11133056), 2010 - 2012 (CHF 110‘000.- Main recipient) : Role of orexin/hypocretin in drug related behaviors.
  • Grant from the Swiss National Science Foundation (3100A-120699), 2008 - 2011 (CHF 318’000.- co-recipient) : Reward-related learning and memory: role of the transcriptional regulators TORC1 and C/EBP, Main recipient: Dr JR Cardinaux.
  • Grant from the Swiss National Science Foundation (3100A0-112101), 2007 - 2010 (CHF 260‘000.- Main recipient) : The hypocretin system and the vulnerability to relapse for cocaine- and ethanol-seeking.

Current projects

  • Role of the hypocretin/orexin system in modulating motivated behaviours (Collaboration with Dr A. Vassalli)
    We studied the motivated behaviour in mice deficient in hypocretin/orexin. This work has allowed us to confirm the key role of this peptidergic system in the regulation of cocaine, alcohol and saccharin intake.
  • Role of astrocytic-derived lactate in the positive long-term memory formation linked to cocaine consumption (Collaboration with Prof PJ Magistretti, Dr. JL Martin)
    This research has led us to demonstrate the key role of lactate in the formation of a positive emotional memory related to cocaine use. By interfering with the production of astrocytic lactate, we have shown that rats and mice lose their preference conditioned to a context previously associated with cocaine intake.
  • Identification of the neurobiological mechanisms related to compulsive eating (Collaboration with Dr JR Cardinaux)
    In continuation of our work on modelling eating disorders in animals, in which we demonstrated that the onset of compulsive disorders food intake was closely linked to the emergence of negative affect (and a vulnerability to develop depressive disorders), we were able to highlight the involvement of several genes potentially responsible for these behavioural disorders. In particular, our results highlight the important role of leptin signaling (particularly in the prefrontal cortex), the transcription factor CRTC1, and Bdnf.
  • Impulsiveness and vulnerability to addiction in juvenile rats
    Numerous clinical and epidemiological studies suggest an excessive drug use during adolescence, and several explanations have been advanced to justify this trend, among which increased sensation-seeking, enhanced impulsivity and a greater influence of peers. Our results indicate that juvenile rats show an increased impulsive behaviour, and a greater persistence to seek a reward compulsively despite mild electric foot shocks. Juvenile rats also exhibit a higher anxiety profile, which can be another source of vulnerability. However, some behavioural characteristics do not suggest vulnerability in juvenile rats. No difference between young and adult rats was found with regard to novelty seeking. In addition, we have shown that adolescent rats allocate less attention to stimuli predicting the availability of rewards, suggesting a lower vulnerability to cue-induced relapse for a previously extinguished reward seeking behaviour. In summary, this study provides an objective evaluation of juvenile behaviours related to reward seeking. Despite elements of vulnerability, adolescent rats do not show any excessive attraction to cocaine, or predisposition to compulsive use of the drug. These observations may constitute a solid rationale for investigating the neurobiological basis of the developing brain, and open a debate on a possible overestimation of the vulnerability of juvenile rats and their human counterparts to develop psychiatric disorders such as drug addiction.

Swiss Collaborations

  • Dr Jean-René Cardinaux, Centre de Neurosciences Psychiatriques, CHUV-DP
  • Prof. Pierre Magistretti, Centre de Neurosciences Psychiatriques et EPFL
  • Dr Anne Vassalli, Centre Intégratif Génomique, Université de Lausanne

International Collaborations

  • Associate Professor Luis de Lecea, Stanford University, Palo Alto, California, USA
  • Assistant Professor Antoine Adamantidis, McGill University, Montreal, Canada
  • Assistant Professor Stephanie Borgland, University of Calgary, Canada

Publications

Original Articles (2008-2013)

  • ROSSETTI C, SPENA G, HALFON O, BOUTREL B. (2013) Evidence for a compulsive-like behavior in rats exposed to alternate access to highly preferred palatable food. Addiction Biology May 9. doi: 10.1111/adb.12065
  • LABOUÈBE G, LIU S, DIAS C, ZOU H, WONG JC, KARUNAKARAN S, CLEE SM, PHILLIPS AG, BOUTREL B, BORGLAND SL (2013) Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids. Nature Neuroscience, 16, 300-308.
  • ADAMANTIDIS AR, TSAI HC, BOUTREL B, ZHANG F, STUBER GD, BUDYGIN EA, TOURIÑO C, BONCI A, DEISSEROTH K, DE LECEA L. (2011) Optogenetic interrogation of dopaminergic modulation of the multiple phases of reward-seeking behavior. J. Neuroscience, 31, 10829-10835.
  • ZORRILLA E, WEE S, ZHAO Y, SPECIO S, BOUTREL B, KOOB GF, WEISS F. (2012) Extended access cocaine self-administration differentially activates dorsal raphe and amygdala corticotropin-releasing factor systems in rats. Addiction Biology 17, 300-308.
  • KARBOUCHE H, STEINER N, MORELATO M, STAUB C, BOUTREL B, MANGIN P, SPORKERT F, AUGSBURGER M. (2010) Influence of ethanol dose and pigmentation on the incorporation of ethyl glucoronide into rat hair. Alcohol 44, 507-514.
  • SPECIO SE, WEE S, O'DELL LE, BOUTREL B, ZORRILLA EP, KOOB GF. (2008): CRF(1) receptor antagonists attenuate escalated cocaine self-administration in rats. Psychopharmacology 196, 473-482.

Review Articles (2008-2013)

Links with the media

Contact

Laboratory on the Neurobiology of Eating and Addictive Disorders
Centre de neurosciences psychiatriques
Site de Cery
CH -1008 Prilly-Lausanne
Tél. +41 21 314 3627
Fax +41 21 643 6950
 Last updated on 30/04/2019 at 14:25