Research Group on Alcohol & Pharmacodependences (GRAP)

Contact name	Email	phone number
JEANBLANC Jérôme	jerome.jeanblanc@u-picardie.fr
NAASSILA Mickaël	mickael.naassila@u-picardie.fr	(+33) 3 22 82 76 72
NGUYEN-KHAC Eric	Nguyen-Khac.Eric@chu-amiens.fr	(+33) 3 22 08 88 51
PIERREFICHE Olivier	olivier.pierrefiche@u-picardie.fr	(+33) 3 22 82 79 32
PRANGER Annick	grap@u-picardie.fr	(+33) 3 22 82 77 58

https://grap.u-picardie.fr/

Université de Picardie Jules Verne – Chemin du Thil

80000 AMIENS

Our research theme is alcohol addiction and alcohol-related liver disease. There are several lines of research: • Individual and environmental factors involved in binge drinking in young people (clinical and animal model studies) • Brain consequences of binge drinking and alcohol addiction (cognitive deficits, including memory processes and synaptic plasticity; psychiatric comorbidities). Modelling binge drinking behaviour in young people. • Somatic consequences of binge drinking and alcohol addiction, in particular: pathophysiological mechanisms of acute alcoholic hepatitis and alcohol-induced hepatocarcinoma. Cellular models allow us to elucidate the mechanisms involved in the aggressiveness of alcohol-related hepatocarcinoma Animal models of binge drinking and alcohol addiction allow us to understand the neurobiology and evaluate the relevance of novel treatments as well as to consider clinical trials in patients with alcohol use disorder and/or alcohol-related liver disease.

Nombre de chercheurs : 12
Nombre de doctorants :
Nombre de personnel d'appui à la recherche : 5
Effectif total : 24

1. SMARTBINGE APP MYDÉFI: Smartphone application for university students with binge drinking behaviour: national randomised controlled trial (https://grap.u-picardie.fr/projets/smartbinge-app-mydefi/) 2. ADELY LSD: Treatment of alcohol dependence with lysergic acid diethylamide (LSD): translational approach and clinical efficacy study (ADELY). (https://grap.u-picardie.fr/projets/adely-lsd/) 3. HEPATALC: Dysbiosis of the intestinal microbiota in acute alcoholic hepatitis: a translational approach. (https://grap.u-picardie.fr/projets/hepat-alc-microbiote/) 4. PREFRONTNALC Preventing binge drinking and alcohol addiction by targeting dopamine D1 and D2 receptor imbalance and medial prefrontal cortex dysfunction. (https://grap.u-picardie.fr/projets/prefrontnalc/)

'1. Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism.Meinhardt MW, Pfarr S, Fouquet G, …, Jeanblanc J,… Naassila M, Spanagel R, Sommer WH.Sci Adv. 2021 Nov 19;7(47):eabh2399. doi: 10.1126/sciadv.abh2399. pdf. 2. Astrogliosis and compensatory neurogenesis after the very first ethanol binge drinking-like exposures in adolescent rat C Vilpoux, G. Fouquet, C. Deschamps, E. Lefebvre, P. Gosset, J. Antol, L. Zabijak, I. Marcq, M. Naassila, O. Pierrefiche2021. Alcohol Clin Exp Res. Doi : 10.1111/acer.14757 3. Mechanisms of chronic alcohol exposure-induced aggressiveness in cellular model of HCC and recovery after alcohol withdrawal. Marié C, Fouquet G, Courtois A, Amrathlal RS, Jankovsky N, Ouled-Haddou H, Tebbakha R, Bouhlal H, Nguyen-Khac É, Naassila M, Marcq I. Cell Mol Life Sci. 2022 Jun 17;79(7):366. doi: 10.1007/s00018-022-04387-y 4. Memory and plasticity impairment after binge drinking in adolescent rat hippocampus: GluN2A/GluN2B NMDA receptor subunits imbalance through HDAC2. Drissi I, Deschamps C, Fouquet G, Alary R, Peineau S, Gosset P, Sueur H, Marcq I, Debuysscher V, Naassila M, Vilpoux C, Pierrefiche O. Addict Biol. 2019 May 6:e12760. doi: 10.1111/adb.12760. 5. Anti-inflammatory drugs prevent memory and hippocampal plasticity deficits following initial binge-like alcohol exposure in adolescent male rats. Deschamps C, Uyttersprot F, Debris M, Marié C, Fouquet G, Marcq I, Vilpoux C, Naassila M, Pierrefiche O. Psychopharmacology (Berl). 2022 Jul;239(7):2245-2262. doi: 10.1007/s00213-022-06112-w You can find all publications here : https://grap.u-picardie.fr/publications/

National : Université de Lille, Université de Rouen Normandie, Université de Caen Normandie, Université de Rennes, Université de Bretagne Occidentale, Nantes Universités International : Université de Camerino, Université de Heidelberg, Université de Nijmegen (Pays-Bas), Université de Leuven (Belgique), Université de Portsmouth (UK)

Bioproject Biotech : Interest of dopamine D3 and histamine H3 receptor modulators in alcohol use disorder.

GRAP's teacher-researchers participate in the teaching of the Pharmacy, Science, Psychology and Medicine departments (and its speech therapy department). Our unit is attached to the Doctoral School Sciences, Technologies, Health ED 585.
Our Unit is responsible for the DU of Addictology and co-leader of the neuroscience course of the MASTER BISA.

Alcohol addiction is a complex behavioural disease whose vulnerability depends on the interaction between genetic and environmental factors. A better understanding of the disease and the search for new treatments cannot be envisaged without the use of animal modelling. Different species are used (rat, mouse) to study the behavioural response to alcohol and addictive behaviour. Sensitivity to the acute effects of alcohol is studied by various tests (locomotion, sedation, ataxia, hypothermia). The same tests can be used with repeated exposure to alcohol to study the phenomenon of tolerance and reverse tolerance (behavioural sensitisation to motor stimulant effects; see ANR project SENSIBALCO). Anxiety-like behaviour is also studied because anxiety is one of the manifestations of withdrawal and may motivate ethanol consumption for its anxiolytic properties. The three tests used are the elevated plus maze, the light-dark box and the open field and thigmotaxis. Cognitive, learning and memory abilities are measured in several tests such as the 8-arm radial maze and novel object recognition. Different cellular models of cancers are used to understand the mechanisms by which chronic exposure to alcohol induces an increase in cancer aggressiveness and the effects of alcohol withdrawal. The other protocol of choice used routinely in the laboratory is that of operant self-administration of ethanol by mouth in Skinner cages. In this procedure the animal has to perform a task to obtain alcohol: pressing a lever or inserting its snout into an orifice. This procedure makes it possible to determine the animal's motivation to consume alcohol because it is possible to increase the "price to pay" progressively during the same session, i.e. each time the animal consumes alcohol, the next one will be more expensive (higher number of presses required to deliver alcohol). In this so-called "progressive ratio" protocol, when the animal "cracks" (stops pressing), the maximum number of presses made to obtain the last alcohol delivery constitutes the "break point", a direct reflection of the animal's level of motivation to consume alcohol. After a learning phase of several weeks, it is possible to subject the animals to a period of abstinence and then relapse induced by different stimuli (alcohol, discriminative stimulus associated with alcohol such as a light signal, stress). To study alcohol addiction, the Unit uses operant alcohol self-administration coupled with the induction of physical dependence through chronic (>7sem) and intermittent (14h/d) exposure to ethanol vapour (40mg/l of air) to achieve target BACs of 1.5 to 2.5g/l. Only this procedure allows the study of the phenomenon of alcohol dependence with the appearance of the neuro-adaptations and the negative emotional state characteristic of addiction. The team can induce addiction in 70 rats and 100 mice simultaneously. Finally, exposure at an early stage of life (in utero and adolescence) is a strong predictor of the risk of developing addiction, but the neurobiological mechanisms remain unknown. The Unit has two early exposure procedures: 1) consumption of a 10% alcohol solution by pregnant and lactating mothers and 2) in adolescence, exposure to massive (3g pure ethanol/kg body weight) and repeated alcohol intoxication. The Unit has recently set up a unique and original model of binge drinking in rats that voluntarily self-administer massive quantities (1 to 3 g of pure ethanol per kilo of body weight) in a record time (15 minutes). This model makes it possible to study the individual and environmental factors involved in this behaviour and also to find effective pharmacological tools. The unit has set up a model of liver damage induced by chronic alcohol consumption in order to study changes in the intestinal microbiota and to test the effectiveness of intestinal microbiota transplantation (on the disease and on the response to treatment).

We provide consulting services related to all our areas of expertise.

• Inserm
• University of Picardie Jules Verne (UPJV)

GDR 3557 - Réseau de l'Institut de Psychiatrie REUNIRA - Réseau national de recherche en alcoologie Collège des addictologues de la Somme Littoral Sud A²M²P - Fédération Hospitalo-Universitaire

• Health and Nutrition
• Food ingredients
• New therapeutic approaches
• Prevention, well-being and the silver economy
• Medicine of the future: new health equipment and e-health