Brain metabolites reflecting neuronal and glial content can be measured with in vivomagnetic resonance spectroscopy (MRS),which has been applied to assess the brain health associated with various drugs of abuse. The specific neurochemical alterations associated withseveral major categories of abused drugs, including those from psychostimulants, inhalants, opiates, alcohol, and cannabis, were reviewed and compared. Sometechnical issues to be considered in the use of MRS to assess brain pathology and the future directions of MRS to assess drugs of abuse were also discussed.
Despite remarkable progress in our understanding of the neurobiological bases of drug abuse, no novel pharmacotherapies have recently been approved to treat substance use disorders (SUDs). Thus, while reformulations of established treatments have either been approved or are currently in late stage development (e.g., sustained release formulations of naltrexone [Vivitrol®] and buprenorphine [Probuphine®]), the development of medications to treat SUDs has lagged well behind other areas of psychiatry. In this chapter, we review some of the factors that have contributed to this dearth of innovative pharmacotherapies. We also review evidence that supports clinical testing of late stage molecules (developed for other indications) acting at two promising targets, as well as novel biological approaches to the treatment of SUDs.
Drug and alcohol dependence affects millions each year. Adolescence is a period of increased risk for substance use disorders. Understanding how the brain is changing during this developmental window relative to childhood and adulthood and how these changes vary across individuals is critical for predicting risk of later substance abuse and dependence. This chapter provides an overview of recent human imaging and animal studies of brain development focusing on changes in corticostriatal circuitry that has been implicated in addiction. Behavioral, clinical, and neurobiological evidence is provided to help elucidate who may be most at risk for developing a substance abuse problem and whenthey may be most vulnerable.
Drug addiction is a chronic brain disease considered to result from a series of transitions from voluntary use in search of a hedonic effect, to loss of control over this behavior, and ultimately to compulsive behavior. Important in the context of mental illness is that substance use disorders are comorbid with many psychiatric diseases, including depression, anxiety and schizophrenia. In current research on addiction, animal models recapitulate the phenotypes contributing to abuse susceptibility through initial drug taking, habitual drug taking, abstinence and finally relapse. These models have begun to unravel the molecular, cellular, and behavioral adaptations regulating addictive behaviors in research which has greatly enriched our understanding of the neurocircuitry mediating learning, motivation, mood and stress. This chapter systematically explores animal models that contribute insights to addiction behaviors including, reward, reinforcement, abstinence, relapse, and susceptibility for initiating additive behaviors.
Drug addiction is an important health and societal issue. Dysregulation of reward, such as increased sensitization of incentive salience or greater sensitivity to the withdrawal from reward-related drug effects, has been implicated in this complex and multifaceted disease. Research from the past several years has de-emphasized the role of dopaminergic function within the basal ganglia in favor of an expanding reward network with extensive connectivity between multiple reward circuit nodes and utilizing multiple transmitter systems. Such a paradigm shift has required a reformulation in understanding the neural mechanisms underlying positive and negative reinforcement. Neuroimaging provides unique opportunities for probing multi-node interactions, and thus can assist in better understanding reward and "anti-reward" mechanisms underlying the normal and addiction phenotype. The goal for future neuroimaging research is to better inform the clinical aspect of drug addiction by determining the propensity to develop drug addiction, assessing severity of addiction, predicting treatment outcome, and facilitating individualized treatment regimens.
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