The consumption of chemical substances that produce transient feelings of euphoria or pleasure and the development of dependence on those substances by a subset of individuals is as old as the human race itself. Currently, the cost of addiction to illicit drugs in the United States is more than 600 billion dollars a year, with profound social and economic impacts. Despite the prevalence and long history of addiction, it is still not clear what neurophysiological processes are involved in the development and progression of addictive disorders. The challenge of current and future studies is to understand how alcohol and drugs alter specific brain systems to influence tolerance and/or lead to the addicted state with the overarching goal of identifying vulnerable populations and improving on current treatment strategies.

Drug addiction is defined as a chronic relapsing disorder that is comprised of three stages: preoccupation/anticipation, binge/intoxication, and withdrawal/negative affect. These three stages are conceptualized as feeding into one other, becoming more intense over time, and ultimately leading to the pathological state known as addiction. Different drugs produce distinct patterns of addiction that engage different components of the addiction cycle, depending on dose and length of use. As an individual moves from being a “user” to “abuser” and then to “addicted” a shift occurs from positive reinforcement driving the motivated behavior to negative reinforcement driving the motivated behavior. Importantly, the progression of drug addiction involves alterations in normal brain circuitry that result in long-lasting drug-induced neuroplastic changes. Critical neurotransmitters (i.e., gamma-aminobutyric acid, glutamate, dopamine, opioid peptides, serotonin, acetylcholine, endocannabinoids, corticotropin releasing factor) and neurocircuits (i.e., ventral tegmental area, nucleus accumbens, amygdala, cerebellum, prefrontal cortex) underlie the pathological changes at each of these stages. A better understanding of the main cellular mechanisms and circuits affected by chronic drug use and the influence of environmental stressors, developmental trajectories, and genetic factors on these mechanisms will lead to a better understanding of the addictive process and to more effective therapeutic strategies for the prevention and treatment of substance-use disorders.

Alcohol and drugs of abuse represent unique experimental challenges as they often engage multiple molecular and intracellular systems in distinct brain regions. Current work seeks to identify these molecular targets and how they are altered by acute and/or chronic exposure. One important molecular target is phosphodiesterase 10A (Pde10a), a regulator of cyclic nucleotide activity. Expression of Pde10a, which is associated with relapse-like ethanol self-administration, was differentially altered during different stages of alcohol withdrawal in the rat. During acute withdrawal Pde10a expression was increased in the basolateral amygdala and medial prefrontal cortex.

International Journal of Emergency Mental Health and Human Resilience, is a multidisciplinary quarterly designed to be the premier international forum and authority for the discussion of all aspects of emergency mental health.

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Regards,

Journal Coordinator

International Journal of Emergency Mental Health and Human Resilience