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Mice lackingCntnap2show abnormal neuronal migration, asynchronous firing patterns and have an autism-like phenotype that can be partially normalized by treatment with risperidone.
Neurogenesis in the subventricular zone is robust in infancy, with cells migrating to olfactory regions and also to the prefrontal cortex, but this declines sharply before the age of two.
Chronic drug exposure induces long-term changes in the brain, which are partly due to alterations in gene expression. Robison and Nestler review the mechanisms by which drugs of abuse alter the transcriptional potential of genes through the regulation of transcription factors and epigenetic mechanisms, including the regulation of gene expression by non-coding RNAs.
The regulation of the hedonic properties of food and addictive drugs involves common neural circuits and molecular substrates. Kenny reviews the shared mechanisms that may contribute to both obesity and drug addiction.
Functional imaging studies have pointed to a key role for the prefrontal cortex (PFC) in addiction, both through its regulation of limbic regions and its involvement in higher-order executive function. Goldstein and Volkow review these studies, showing that disruption of the PFC in addiction not only underlies compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of non-drug related motivation and self-control.
Current addiction pharmacotherapies have limited success. Focusing on alcohol addiction, Heilig and colleagues review the evidence that genetic heterogeneity in the opioid, corticotropin-releasing factor, GABA and serotonin systems may underlie differential treatment responses, and that personalized therapies tailored to patient genotype may lead to more successful treatment for alcohol addiction.
Current theories of addiction all argue for a unitary account of drug addiction. Badiani and colleagues challenge this view by highlighting behavioural, cognitive and neurobiological differences between opiate addiction and psychostimulant addiction. They argue that these differences have important implications for addiction treatment, addiction theories and future research.
Addiction incurs enormous medical, economic and social costs. The currently available pharmacotherapies for addiction are only moderately effective, which further emphasizes the need to improve our understanding of the changes that are induced in the brain by addictive substances. This Focus issue features five articles that discuss recent insights into the neurobiology of addiction — from the molecular to the behavioural level — and highlight the importance of these findings for the development of new treatments.