Drug addiction is defined as a chronic relapsing disorder characterized by persistent drug-seeking and drug-taking behaviors, and it 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, corticotrophin releasing factor) and neurocircuits (i.e., ventral tegmental area, nucleus accumbens, amygdala, cerebellum, prefrontal cortex) underlie the pathological changes at each of these stages. The mission of the current neurobiology of addiction field is to understand the neuropharmacological and neuroadaptive mechanisms within the brain that mediate the transition between occasional controlled drug use and the loss of control in drug taking and possibly indentify populations that may be more vulnerable to the effects of certain drugs and/or at risk for developing addiction. A better understanding of the main cellular mechanisms and circuits affected by chronic drug use and the influence of enviromental 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. In this special topic, we will provide various important breakthroughs on the actions of commonly abused addictive substances (i.e., alcohol, cocaine, nicotine, cannabinoids) on the function of neuronal circuits. Together this work represents the most current understanding of how acute and/or chronic exposure to various abused substances engage and/or pathologically alter distinct brain circuits.

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