Stub body
Research
Our research is interested in the neural, cellular and molecular substrates of inter-individual vulnerability to develop impulsive / compulsive disorders such as drug addiction or Obsessive - compulsive disorder. Our working hypothesis is that impulses, originating from the amygdalo insular networks can drive the behavior through explicit knowledge involving prefrontal and orbitofrontal loops or implicit mechanisms that instead depend upon the functional relationships of these structures with several domains of the striatum.
We suggest that inter-individual vulnerability to develop impulsive / compulsive neuropsychiatric disorders stem from aberrant plasticity processes within the corticostriatal networks governing the translation of impulses into actions that ultimately result in a so-called abnormal incentive habit process.
Our research is designed according to a vertical, top-down strategy with direct translational perspectives. It stems from a unique combination of contemporary techniques ranging from experimental psychology to causal manipulations of the brain with selective pharmacological tools, DREADDS or optogenetics and,correlational analyses of the brain using state of the art molecular biology and electrophysiology techniques.
Our program is subdivided in several converging lines of research:
1. The role of the insular cortex, and its interactions with the BLA and the ventral striatum, in drug addiction and OCD.
2. The nature of the functional interactions between the amygdala and the striatum subserving the establishment of compulsive incentive habits.
3. The cellular and molecular substrates of intrastriatal shifts subserving incentive habits habits.
4. The influence of the environment on inter-individual differences in the vulnerability to develop impulsive / compulsive disorders.
Techniques and approaches:
1. Behaviour: characterisation of inter-individual differences in:
- State of the art chronic cocaine, heroin or alcohol self-administration in the rat measuring reinforcement, escalation, but also drug seeking, may it be goal-directed, habitual or compulsive, using sophisticated schedules of reinforcement and preclinical models
- Compulsive behaviour, as measured in a Schedule-Induced polydipsia procedure
- Impulsivity, as measured in the 5-Choice Serial reaction Time Task, DRL, FCN and delay discounting task
- Decision making, as measured in a Rat Gambling Task
- Anxiety, as measured in Open fields and Elevated Plus Maze
- Locomotor reactivity to novelty, and novelty preference, as measured in novelty-induced CPP tasks
- working memory and behavioural flexibility, as measured in T-maze based tasks and operant tasks
- Sign tracking
- Drug discrimination
2. Circuits
2.i Causal manipulations of the brain in freely moving rats, including:
- Chemo- and optogenetic manipulation of specific pathways
- Pharmacological manipulation of specific brain regions using intracerebral infusions
2.ii In vivo electrophysiological recording of single units and LFPs in anaesthetised rats
3. Cellular and Molecular Biology
- in situ hybridisation
- RNAscope
- qPCR
- western-blot
- cell culture
- immunohistochemistry
Publications
Daniel ML, Cocker PJ, Lacoste J, Mar AC, Houeto JL, Belin-Rauscent A & Belin D (2017) The anterior insula bidirectionally modulates cost-benefit decision making on a rodent gambling task, EJN, 10.1111/ejn.13689
Murray JE, Belin-Rauscent A, Simon M, Giuliano C, Benoît-Marand M, Everitt BJ* & Belin D* (2015) Differential role of the basolateral and central amygdala in the recruitment and maintenance of dorsolateral striatum-dependent cocaine seeking habits. Nature Communications (6), doi:10.1038/ncomms10088. *: co last authors
Ducret E, Puaud M, Lacoste J, Dugast E, Belin-Rauscent A, Murray JE, Everitt BJ, Houeto JL & Belin D (2015) N-acetylcysteine-induced increased sensitivity to adverse consequences in rats with escalated cocaine intake is associated with parallel cellular plasticity mechanisms in the ventral and dorsolateral striatum. Biological Psychiatry, doi:10.1016/j.biopsych.2015.09.019
Belin-Rauscent A, Daniel ML, Puaud M, Jupp B, Sawiak SJ, Howett D, McKenzie C, Caprioli D, Besson M, Robbins TW, Everitt BJ, Dalley JW & Belin D (2015) From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive disorders. Molecular Psychiatry, doi:10.1038/mp.2015.140
Belin D, Belin-Rauscent A, Murray JE, Everitt BJ (2013) Drug addiction: a failure in regulation maladaptive incentive habits. Current Opinion in Neurobiology, 23 (4), 564-572; DOI:10.1016/j.conb.2013.01.025
Besson M, Pelloux Y, Dilleen R, Theobald DT, Lyon A, Belin-Rauscent A, Robbins TW, Dalley JW, Everitt BJ; Belin D. (2013) Cocaine modulation of fronto-striatal expression of zif268, D2and 5-HT2c receptors in high and low impulsive rats. Neuropsychopharmacology, 38(10):1963-73. doi:10.1038/npp.2013.95
Belin D, Mar AC, Dalley JW, Robbins TW and Everitt BJ (2008) High impulsivity predicts the switch to compulsive cocaine taking. Science, 320(5881): 1352-1355.
Belin D and Everitt BJ (2008) Cocaine-Seeking Habits Depend upon Dopamine-Dependent Serial Connectivity Linking the Ventral with the Dorsal Striatum. Neuron, 57:432-441
Deroche-Gamonet V, Belin D, Piazza PV (2004) Evidence for addiction-like behaviour in the rat, Science 305(5686):1014-7
Current Lab Members:
Lab manager: Mickaël Puaud
Research Associates:
Dr Chiara Giuliano
Dr Aude Belin-Rauscent
Dr Lucia Marti-Prats
Dr Paul Cocker
Dr Clara-Velazquez-Sanchez
Dr Toni Ferragud (co-supervised by Dr Milton)
PhD students:
Maxime Fouyssac
Tish Ward
Aïcha Aleian
Alumni:
Dr Marie-Laure Daniel
Dr Jean-Yves Rotgé
Dr Jennifer Murray
Dr Solène Ansquer
Ritchy Hodebourg
Katie Cudmore