Neural Basis of Drug Addiction
Barry Everitt, University of Cambridge
Description: How does someone move from recreational drug use to addiction? Barry Everitt's group at the University of Cambridge has been trying to break down the stages and neural circuitry of addiction with great precision.
Everitt's research attempts to operationalize a progression in animals from the voluntary taking of drugs, to the acquired habit of drug"taking, to the stage of compulsive drug"seeking and consumption, "where individuals have really lost control." This progression seems rooted in the sequential activation of different learning systems in the brain, which are particularly sensitive to the neurotransmitter dopamine.
Research suggests that drug"taking is initially dependent on the nucleus accumbens (part of the ventral striatum), but its establishment involves the dorsal striatum. Studies show that dopamine in the dorsal striatum is causally involved in establishing drug"seeking behavior in rats. As the animal gets accustomed to taking the cocaine, there's a "shift in the balance of associative encoding from ventral to dorsal striatum." Cocaine craving and self"administration seem to change the functioning of the dorsal striatum in monkeys and humans as well.
While this shift from ventral to dorsal striatum depends to some degree on "pharmacology" (cocaine's impact on dopaminergic systems), Everitt has hypothesized that it may also involve "spiraling circuitry" connecting the ventral striatum, the midbrain -- the brain's motivational and motor mechanisms -- and the dorsal striatum. Everitt speculates that the compulsive nature of drug seeking may be rooted in part in the prefrontal cortex, home to "top"down executive control mechanisms." He describes research that attempted to model this type of compulsion. Animals with short"term access to cocaine and most animals with long"term access to cocaine suppressed their drug"seeking responses when punished. But a subgroup of 20% "persisted in seeking cocaine in the face of punishment." This result has been replicated many times now, and turns out to have a parallel among humans. This, says Everitt, "brings up the issue of vulnerability to drug addiction."
Additional research suggests that impulsivity is a "behavioral characteristic that predicts the transition from initial drug intake to loss of control to compulsive seeking and taking" of drugs. Highly impulsive animals denied cocaine become more impulsive and drug seeking over time, leading to relapses. Everitt and others are tracing the neural basis of compulsivity to impairment in the prefrontal cortex, which involves "a loss of control over maladaptive habits" established after long"term drug taking.
About the Speaker(s): Barry Everitt graduated in Zoology and Psychology at Hull University, received a Ph.D. from the University of Birmingham, and undertook post"doctoral research at Birmingham and at the Karolinska Institute in Stockholm. He was appointed to the Department of Anatomy at the University of Cambridge in 1974, became a Fellow of Downing College in 1976, a tenured University Lecturer and a Director of Studies in medicine at Downing in 1979. He has served on several national and international advisory committees and has been President of the British Association for Psychopharmacology, the European Brain and Behaviour Society and the European Behavioural Pharmacology Society. He is a Fellow of the Royal Society, a Fellow of the Academy of Medical Sciences, and has been awarded an Honorary D.Sc. by Hull University.
Everitt's research concerns the neural and psychological mechanisms underlying learning, memory motivation and reward. Much of his current research involves the neuropsychology of drug addiction, especially drugs such as cocaine and heroin. A major research theme is the impact of learning on drug addiction " both its development and its persistence.
Host(s): School of Science, McGovern Institute for Brain Research at MIT
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