Dept. of Psychiatry
300 George Street
New Haven, CT
06511 USA
Tel: 203-785-2117
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Clinical and Basic
Neuroscience Research
Training Program in Psychiatry
Substance Abuse Research Leading to Clinical Breakthroughs
The personal and societal costs of drug addiction are considerable, with an estimate 1 million people entering the medico-legal systems as a result of their dependence. Thus, drug addiction research has been an important focus of Yale's clinical and basic neuroscience research, in hopes of improving our understanding the neurobiological underpinnings of the vulnerability to drug abuse and the brain mechanisms of drug reinforcement.
Based on basic electrophysiological studies in the early 1970s, researchers characterized the cellular actions of commonly abused drugs in discrete brain regions, including those mediating the physical and psychological effects of opiates and hallucinogens.
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At the molecular level, a focus on mesolimbic dopamine systems and their projections to the nucleus accumbens are pointing to important predisposing factors and consequences of drug abuse. At the clinical levels, pharmacological strategies for antagonizing cocaine's acutely reinforcing and euphorigenic properties are underway.
Current cutting-edge interests in people and laboratory animals include the well-known cross-sensitization between stress, psychostimulants, and other drugs of abuse. Such studies are suggesting common biochemical pathways that mediate both environmental and genetic responses to drugs of abuse. These studies have exciting implications for understanding not only problems of chemical dependency and drug abuse, but other stress-mediated phenomenon as well.
Studies elucidating noradrenergic neurophysiology in the nucleus locus coeruleus and its role in mediating the phenomenon of physical dependence to chronic opiate exposure have led in the past decade to the successful clinical application of the alpha-2 receptor agonist, clonidine, in the treatment of opiate withdrawal. Similarly, laboratory studies into benzodiazepine (i.e, valium) receptor regulation are now generating rapid clinical detoxification methods for humans dependent on sedative-hypnotic drugs.
Presently, both clinical and basic neuroscience researchers are attempting to understand the genetic basis for the vulnerability to psychoastimulant addictino. At the basic level, transgenic animal models (including inducible and consituitive gene knock-outs and knock-downs) are being exploited. In conjunction with these advances, clinical researchers are performing human genetic studies of psychostimulant abusers, including candidate gene / polymorphism based association studies and whole-genome scanning / linkage-based approaches.
Faculty related to Substance Abuse Research
Alreja
Gelernter
Kosten, Therese
Picciotto
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