Neuronal Substrates of Socially-Induced Alcohol Drinking Underlying Vulnerability to Addiction in rats

The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master's degree in a non-French university.

This project is one of the proposed projects. Not all proposed projects will be funded, check our website for details.

State of the art: Only a subset of alcohol users develops compulsive use, yet the social contribution to this vulnerability remains unexplored. Alcohol consumption is most often initiated in social contexts, but rodent models of alcohol use disorders (AUD) are typically conducted in controlled tasks with isolated animals, thus limiting investigation on the social influences on addiction vulnerability. The prefrontal cortex (PFC) regulates executive control and social behaviors and is strongly affected by chronic ethanol exposure. Its projections to the nucleus accumbens (NAcc) are central to reward processing and relapse, while those to the subthalamic nucleus (STN) drive decision-making and inhibitory control. However, the role of these pathways in socially-induced voluntary alcohol intake remains poorly characterized.

Objectives: (1) Determine how social interactions influence voluntary alcohol intake and vulnerability to AUD, and how chronic ethanol consumption reorganizes social dynamics in groups of males or female rats. (2) Characterize intrinsic and synaptic electrophysiological properties of PFC-Nacc and PFC-STN projecting neurons in socially ethanol-exposed rats. (3) Manipulate the activity of these projections using chemogenetic approaches (DREADDs) to modulate social behaviors to promote or prevent ethanol intake and AUD vulnerability.

Methods: The ‘Live Rat Tracking’ (LRT) system will monitor naturalistic social behaviors in groups of rats for several days, during which they will have an intermittent access to ethanol to assess voluntary drinking and AUD. Ex vivo recordings (excitability, synaptic transmission…) will be performed after the ethanol ± LRT protocols in rats previously injected with two distinct Alexaconjugated Cholera Toxin B retrograde tracers in the NAcc and STN to identify of mPFC-Nacc and -STN projecting neurons. PFC pathways will be modulated using a DREADD Cav2-Cre viral strategy, with the DREADD agonist added in the LRT tap water to allow sustained activation/inhibition of the pathways.

Expected results: Preliminary results showed that alcohol voluntary intake is higher in female than male rats, and that alcohol consumption alters established social dynamics. We expect to identify social patterns predictive of alcohol intake and AUD vulnerability, associated with alterations in PFC pathways in vulnerable versus resilient animals. DREADD modulation of PFC projections is expected to affect social influences that facilitate drinking or strengthen protective social dynamics.

Feasibility: The team has all necessary equipment, expertise and ethical authorization (APAFIS #46528) to efficiently execute the project.

Complementarity of the two co-supervisors: C. Beurrier and M. Degoulet (CoPhyBaG) will join their complementary skills and expertise in ex vivo electrophysiology and addiction-like behavioral approaches in rats. 

Within Aix Marseille Université, NeuroMarseille brings together 8 research laboratories and NeuroSchool, a graduate school in neuroscience, to increase the attractiveness of the university, international collaborations, interdisciplinarity, links with the clinical and industrial worlds and the integration of students into professional life. 

Launched in July 2018, NeuroSchool unifies and harmonizes the training of the third year of the Bachelor of Life Sciences (Neuroscience track), the Master's and the PhD in Neuroscience. 

• Expected candidate profile:

1.  strong interest in social and addiction-like behaviors;
2. experience with rodent handling and behavioral paradigms;
3. coding skills;
4. knowledge of electrophysiology, histology, or viral tracing.