Addiction and its brain science Rainer Spanagel1 & Markus Heilig2

Addiction can best be defined as a behavioral syndrome, characterized by compulsive drug seeking with repeated relapses into drug use. Addictive behavior may even recur after many years of abstinence in spite of obviously disastrous consequences for the individual, including his death. Other phenomena, such as physical dependence and withdrawal, have to be strictly separated from addictive behavior as an individual can be physically dependent on a drug without being addicted to it and vice versa. In fact, transient and demonstrably reversible adaptive processes within the central nervous system (CNS) and other physiological systems underlie physical dependence and tolerance to a drug. Also, addicted patients do not typically relapse while in a state of withdrawal. Instead, most relapse events occur when withdrawal symptoms have long dissipated. Clearly, more persistent, perhaps irreversible changes within specific neuronal systems must bring about addictive behavior. Among these neuronal systems, the last two decades have seen a tremendous focus on those which mediate positive drug reinforcement as the underpinnings of addiction. One of the major findings to have been observed is that the mesolimbic dopamine system constitutes the core brain reinforcement system, which highlights and predicts important environmental stimuli. Indeed, blockers of the dopamine system induce a 'lock-in situation' in humans, in which relevant environmental stimuli are no longer salient to the organism. Also, drug stimuli and conditioned stimuli that become associated to drug-taking behavior beget their salience to the organism through the mesolimbic dopamine system (Spanagel & Weiss 1999). Further, studies on the interaction of drugs of abuse and the mesolimbic dopamine system have additionally furnished a major hypothesis in the neurobiology of addiction, suggesting that irreversible synaptic alterations on the molecular and/or structural level (i.e. persistent drug-induced synaptic plasticity within the dopaminergic reinforcement system) may underlie addictive behavior. http://www.blackwell-synergy.com/doi/full/10.1111/j.1360-0443.2005.01260.x