Addictive Disorders

May 12-20

Coordinator: George F. Koob

The Scripps Research Institute, La Jolla, USA

Faculties include (partial list):

Antoine Bechara, University of Southern California, Los Angeles, USA

Peter W. Kalivas, Medical University of South Carolina, USA

Christian Luscher, University of Geneva, Switzerland

Barbara Mason, The Scripps Research Institute, La Jolla, USA

Luigi Pulvirenti, The Scripps Research Institute, La Jolla USA

Rainer Spanagel, Central Institute for Mental Health, Mannheim, Germany

Nora Volkow (video presentation), NIDA, Bethesda, USA

Drug addiction is a chronically relapsing disorder that has been characterized by compulsion to seek and take the drug, loss of control in limiting intake, and emergence of a negative emotional state reflecting a motivational withdrawal syndrome when access to the drug is prevented. Drug addiction has been conceptualized as a disorder that involves elements of both impulsivity and compulsivity that yield a composite addiction cycle. Lectures of the Course will cut across multiple aspects of the addiction field to address important emerging areas. Important focus will be:

Pathophysiology of addictive disorders

Neural plasticity during addiction and its significance for therapy

Pathology of motivation and choice in addiction

Emotion, decision-making and substance abuse

Neurobiology of impaired insight in addictive disorders

Animal and human imaging studies have revealed discrete circuits that mediate different stages of the addiction cycle with key elements of the ventral tegmental area and ventral striatum as a focal point for the binge/intoxication stage, a key role for the extended amygdala in the withdrawal/negative affect stage, and a key role in the preoccupation/anticipation stage for a widely distributed network involving the orbitofrontal cortex–dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control. The transition to addiction involves neuroplasticity in all of these structures that may begin with changes in the mesolimbic dopamine system and a cascade of neuroadaptations from the ventral striatum to dorsal striatum and orbitofrontal cortex and eventually dysregulation of the prefrontal cortex, cingulate gyrus, and extended amygdala. The neurochemical and neuroanatomical basis of compulsivity and impulsivity during the course of addiction will represent another major focus with sessions in search for the "neural switch" underlying transition from actions to habits to compulsions.

The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.

The primary behavioral pathology in drug addiction is the overpowering motivational strength and decreased ability to control the desire to obtain drugs. Advances in neurobiology are now approaching an understanding of the cellular and circuitry underpinnings of addiction, and they describe the novel pharmacotherapeutic targets emerging from this understanding Addiction is associated with neuroplasticity in the corticostriatal brain circuitry that is important for guiding adaptive behaviour. The hierarchy of corticostriatal information processing that normally permits the prefrontal cortex to regulate reinforcement-seeking behaviours is impaired by chronic drug use. A failure of the prefrontal cortex to control drug-seeking behaviours can be linked to an enduring imbalance between synaptic and non-synaptic glutamate, termed glutamate homeostasis. The imbalance in glutamate homeostasis engenders changes in neuroplasticity that impair communication between the prefrontal cortex and the nucleus accumbens. Some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction.

Emerging cognitive studies have recently provided great impulse to the understanding of addictive disorders. Imaging studies have contributed to link a number of brain regions to specific aspects of the addictive cycle. For example, while the insula appears to be critical in interoception, self-awareness and drug craving, the anterior cingulate cortex mediates behavioral monitoring and response selection and the dorsal striatum is critical for automatic habit formation. Emerging evidence in now pointing at specific brain structures that underlie how drug-related stimuli predict emotional behavior in addicted individuals, even without conscious awareness.

During the Course a wide range of additional topics will be analyzed in depth in order to address the current and future challenges of drug abuse research. The opiate system will be another specific focus and the genetic basis of neuroadaptation during opiate abuse will be addressed: particular attention will be devoted to the significance of studies that use multiple technique including in vitro and in vivo mutagenesis with pharmacological aproaches, cellular imaging and behavior. New vistas in understanding and treating alcohol dependence also will be discussed. Here specific sessions will be dedicated to the most recent advances in pharmacology and the potential for developing drugs of clinical efficacy.

For all sections of this Course a strong emphasis will be placed on critical analysis. Participants will be provided with a thorough understanding of frontiers of the genetic/epigenetic, cellular, and molecular mechanisms that mediate the deveopment of addictive disorders and the loss of behavioral control over drug-seeking and drug-taking. Plenty of discussion will be devoted to new technologies and to research that defines new directions and the Course will altogether provide an essential framework for anyone involved in the field of addictive disorders.