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Unformatted text preview: 2007 Nature Publishing Group More than a century ago, Ramon y Cajal speculated that information storage in the brain results from alterations in synaptic connections between neurons 1 . The discov- ery in 1973 of long-term potentiation (LTP) of glutamate synapses in the hippocampus 2 launched an exciting exploration into the molecular basis and behavioural correlates of synaptic plasticity. Partly because LTP was first described at synapses in the hippocampus, a brain region necessary for declarative memory formation, there was an early assumption that synaptic plasticity represents a cellular building block used exclusively for learning and memory. However, it has since become clear that LTP and its counterpart, long-term depression (LTD), are basic properties of most excitatory syn- apses throughout the CNS, and are used for multiple brain functions in addition to learning and memory 3 . For example, LTP and LTD appear to be essential in the stabilization and elimination of synapses during the developmental fine-tuning of neural circuits in many areas of primary sensory cortex 4 . It therefore may not be surprising that evidence accu- mulated over the last decade demonstrates that drugs of abuse can co-opt synaptic plasticity mechanisms in brain circuits involved in reinforcement and reward process- ing. Indeed, an influential hypothesis is that addiction represents a pathological, yet powerful, form of learning and memory 510 . Although the brain circuitry underlying addiction is complex, it is unequivocal that the mesolim- bic dopamine system, consisting of the ventral tegmental area (VTA) and nucleus accumbens (NAc), as well as associated limbic structures (FIG. 1) , are critical substrates for the neural adaptations that underlie addiction. It is also clear that the interactions between addictive drugs and synaptic plasticity in different brain regions will con- tribute to specific aspects of addiction, such as craving, withdrawal and, perhaps most importantly, relapse. Addiction is not triggered instantaneously upon exposure to drugs of abuse. It involves multiple, com- plex neural adaptations that develop with different time courses ranging from hours to days to months (BOX 1) . Work to date suggests an essential role for synaptic plasticity in the VTA in the early behavioural responses following initial drug exposures, as well as in triggering long-term adaptations in regions innervated by dopamine (DA) neurons of the VTA 9 . By contrast, downstream synaptic changes in the NAc and other brain regions, are likely to represent the formation of powerful and persistent links between the reinforcing aspects of the drug experience and the multiple cues (both internal and external) associated with that exp- erience 510 . Here we review emerging evidence that addictive drugs elicit or modify synaptic plasticity in many of the key brain regions involved in addiction, and that these synaptic modifications have important behavioural consequences. A major motivation for behavioural consequences....
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This note was uploaded on 12/02/2009 for the course PSB 4434 taught by Professor Rowland during the Spring '09 term at University of Florida.
- Spring '09