Eric Nestler, Icahn School of Medicine at Mount Sinai, New York, USA
Peter Kalivas, Medical University of South Carolina, Charlottesville, USA
Christian Luscher, University of Geneva, Switzerland
Yasmin Hurd, Icahn School of Medicine at Mount Sinai, New York, USA
David Belin, University of Cambridge, UK
Marisela Morales, National Institute on Drug Abuse, Bethesda, USA
Caryn Lerman, University of Pennsylvania, Philadelphia, USA
Substance use disorders represent one of the most devastating diseases of modern society. The main goal of the presentations from our world-class scientists is to provide a broad, comprehensive overview of the cutting edge research and findings that have been generated through the many techniques and approaches that they routinely employ. The presentations will discuss the most recent epigenetic, genetic, optogenetic, cellular, synaptic and molecular studies that have been performed in order to elucidate the fundamental mechanisms underlying substance use disorders, but there will also be emphasis on the emerging therapies such as rTMS and DBS. For these reasons, the course should be of interest to a wide range of scientists.
Finally, during all sections of this Course, a strong emphasis will be placed on open, interactive discussions, and strong encouragement will be given to participants to interact as much as possible with the Faculty.
Here follows a brief description of the main theme of each speaker, listed in alphabetical order:
Environmental and behavioural factors of inter-individual differences in drug addiction: from habits to compulsivity
Drug addiction results from the interaction between a vulnerable individual, a drug and an environment which interactions and their contribution to the transition from volitional to compulsive drug seeking habits, the hallmark of addiction, are yet to be understood. However, over the last decade the development of novel preclinical models of addiction in rodents, factoring in the notion of inter-individual differences with the operationalisation of the main clinical features of addiction in humans have helped shed a new light on the mechanisms subserving this inter-individual vulnerability to develop compulsive drug seeking habits. Dr. Belin will review the psychological constructs of the most recent preclinical models of addiction and investigate the recent breakthrough in the psychological and neural substrates of the propensity to use drugs and to switch from controlled drug use to maladaptive drug seeking habits.
In this process, Dr. Belin will especially discuss the role of dynamic functional shifts within the corticostriatal circuits that subserve the development of drug seeking habits and investigate a fundamental question: what are the psychological and underlying neural mechanisms over which control is lost in addiction.
From optogenetics to novel therapies against drugs of abuse
The main goal of Dr. Bonci's presentations will be to discuss the role of long-term plasticity at excitatory synapses in the limbic system in modulating the development and expression of cocaine-dependent behaviors, in order to produce novel therapeutic strategies that could reverse these long-term synaptic changes, and as a consequence, drug-dependent behaviors. Furthermore, during his lecture, he will present published and unpublished results on the basic mechanisms that underlie cocaine-dependent plasticity, and the promising results from clinical studies that were developed based on his laboratory's optogenetic studies.
Neurobiological pathways of addiction risk and treatment implications
Dr. Hurd will present data obtained using multidisciplinary research approaches conducted in animal models and human subjects that expand knowledge about neurobiological processes linked to addiction vulnerability. The discussion will provide insights regarding gene transcription, epigenetic mechanisms, genetics and neural circuits involved in addiction risk with particular focus on the long-term impact of developmental cannabis exposure. Molecular strategies, neuroimaging modalities and behavioral approaches to be discussed include cell-specific RNA-sequencing, chromatin accessibility across the genome, chemogenetics (designer receptors exclusively activated by designer drugs; DREADD) and DREAMM (DREADD-Assisted Metabolic Mapping). Results gleaned from the various lines of research will be discussed in relation to the development of novel treatment strategies.
Using the neurobiology of intrusive thinking to treat drug addiction
During his presentations, Dr. Kalivas will explore the neurocircuitry of how environmental cues initiate pathological motivation to relapse to drug use. He will also discuss how synaptic changes in this circuit dynamically and transiently change in response to drug cues in a manner that potentiates the intrusive nature of drug cues compared to natural motivating stimuli. These studies greatly help us understanding the circuitry and synaptic alterations mediating relapse, and reveal a number of pharmacotherapeutic targets. The utility of each target for treating addiction and the clinical trials conducted to date using this strategy will be explored in the final part of his talk.
Cognitive neuroscience of nicotine addiction
An important limitation of currently available treatments for addiction is they do not tackle the disruptive brain processes that undermine sustainable behavior change. Addictive behaviors like tobacco use are associated with cognitive impairments and altered brain functions that can interfere with the maintenance of goal-directed behaviors. Harnessing and merging novel concepts and tools from the fields of neuroscience, pharmacology, and behavioral science, this presentation will focus on cognitive neuroscience approaches to understanding and treating tobacco dependence.
The emergence of a circuit model of addiction
Dr. Luscher will review cell type-specific optogenetic manipulations that have allowed to identify addiction relevant circuits with to goal to establish links of causality between drug-evoked synaptic plasticity and drug-adaptive behaviors. Dr. Luscher will also explore the claim that the emergence of a circuit model for addiction may open the doors for novel therapies.
Insights to drug addiction derived from brain ultrastructural analysis in the area of optogenetics
Recent findings indicate that there is a great phenotypic variability among dopamine neurons of the ventral tegmental area (VTA); some of these neurons have the capability to use either glutamate or GABA as co-transmitters. I will present recent advances in our understanding of neuronal diversity among VTA-dopamine neurons obtained by combining brain ultrastructural analysis and optogenetics. These findings will be discussed in the context of 'multiplexed' neurotransmission and its possible involvement in the neurobiology of drugs of abuse.
Transcriptional and Epigenetics Mechanisms of Addiction
Dr. Nestler's group is studying chromatin modifications as crucial regulatory mechanisms underlying long-lasting adaptations to drugs of abuse within the brain's reward circuitry. They are using next generation sequencing methods, RNA-seq and ChIP-seq—the latter focusing on numerous histone modifications and regulatory enzymes, DNA methylation, chromatin remodeling proteins, and transcription factors—to obtain a more complete view of drug-induced changes in gene expression in these brain regions. These unbiased approaches can now be mined to develop improved diagnostic tests and treatments for addictive disorders.