Animal Models of Drug Addiction in Support of Novel Therapeutic Strategies

A ddictions to a variety of substances both licit (e.g., alcohol, nicotine) and illicit (e.g., marijuana, cocaine) are a pervasive national and international social and economic challenge, accounting for as much as $600 billion annually in cumulative losses in the United States (cited in Nicholson and Ator 2011). The treatment of addictions and addictive behaviors is thus an important public health concern. Basic animal studies have greatly contributed to progress in this area and will surely continue to yield signifi cant insights into the neuroanatomical circuitry, neurophysiological function, neurochemical changes, and behavioral processes underlying addiction. Current clinical neurobiological methods such as brain imaging have expanded knowledge and provided novel insights into the most complex human brain-behavior interactions. The science of addiction is revealing that alterations of brain-behavioral processes can have a complex mixture of intrinsic and extrinsic causes. A better understanding of the etiology and brain mechanisms directly involved will provide more effective addiction prevention and treatment approaches. The topic is critically important and broad enough to warrant two issues, in which experts review efforts both to understand a variety of substance dependences and to develop therapeutic treatments for them. In this issue the authors address addictions to alcohol, nicotine, marijuana, opiates, cocaine, methamphetamine, and ketamine. Articles in the subsequent , companion issue will focus on the neurobiology of addiction-like behaviors, addressing addiction and psychiatric disorders, sex differences in addiction, and various aspects of food addiction. Each issue also includes an article on IACUC considerations relevant to addiction-related research. Overview Substance addiction is a chronic relapsing brain disorder that results in the addicted individual's inability to limit drug consumption despite detrimental consequences (Meyer 1996). Although initially an individual's substance use is voluntary, with repeated use the brain's reward system is commandeered and neuroadaptive alterations render the individual unable to withstand the irresistible urges to use substances and therefore chronically susceptible to relapse. The slippery slope of drug addiction may start with experimentation or social use to experience the positive reinforcing (euphoric) effects, and then spirals downward in a pattern of abuse—from escalating compulsive drug seeking and taking in an attempt to alleviate the undesirable negative effects (e.g., dysphoria, anxiety, stress), to dependence, and then to withdrawal and abstinence, during both of which relapse to compulsive use is likely (Koob and Le Moal 1997). Understanding vulnerability to relapse as an integral part of addiction is crucial to the effective treatment of …