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How do drug-associated contexts drive behaviour? The role of entorhinal circuitry in addiction

Project description

Evidence-based drug addiction therapies

Drug addiction exacts a staggering toll on society, with its pervasive neuropathological grip fuelling devastating personal and societal costs. The heart of this formidable challenge lies in the persistent tendency for relapse, particularly in environments linked to drug use. With this in mind, the ERC-funded DrugsAndMemory project aims to revolutionise our understanding and treatment of addiction. By unravelling the intricate neural circuitry connecting the motivation to consume drugs with the spatial and non-spatial facets of drug-associated contexts, this project promises groundbreaking insights crucial for preventing and reversing context-triggered drug-seeking behaviour. By employing cutting-edge techniques, including in vivo recordings and optogenetics, the project decodes the complex interplay of spatial and non-spatial cues driving drug-seeking behaviour.


Addiction to drugs is a ubiquitous neuropathological disease that inflicts immense societal costs. A core aspect of addiction that poses a major challenge for treatment is the propensity to relapse in environmental contexts that are associated with drug use. Identification and mechanistic characterization of novel addiction-relevant circuitry linking the motivation to take drugs to the complex spatial and non-spatial features that constitute a drug-associated context are at the core of this proposal. These insights will be used to identify the best constellation of anatomical targets to prevent and reverse the expression of context-triggered drug-seeking. The medial and lateral entorhinal cortex (MEC and LEC) are two central components of the episodic memory system integrating all features relevant for the formation of contextual memory. Crucially, MEC and LEC receive strong bottom-up dopaminergic input from the midbrain and send top-down projections to the nucleus accumbens (NAc). The dopaminergic system is the primary target of all addictive drugs. We will 1) study how bottom-up dopaminergic projections are implemented into drug-context associations in MEC and LEC and 2) determine how these associations influence NAc-mediated drug-seeking behaviour. We will utilize a multidisciplinary approach by developing electrophysiological in vivo recording paradigms in behaving mice that allow the assessment of complex spatial, contextual and non-spatial codes in conditioned place preference and self-administration paradigms typically used to model addiction in rodents. This will be combined with optogenetically-assisted circuit analysis of molecularly-defined pathways to link identified functions to the underlying circuitry. Pathway-specific optogenetic silencing will be used to prevent and reverse the manifestations of drug use on a neuronal and behavioural level. This will guide the evidence-based development of therapies in the future, such as deep-brain stimulation.

Host institution

Net EU contribution
€ 1 498 475,00
69120 Heidelberg

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Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Higher or Secondary Education Establishments
Total cost
€ 1 498 475,00

Beneficiaries (1)