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PERSPECTIVENEUROBIOLOGY OF ADDICTIONIs there a common molecular pathway for addiction?.com/natureneuroscienceEric J Nestlerhttp://www.natureDrugs of abuse have very different acute mechanisms of
action but converge on the brains reward pathways by
producing a series of common functional effects after both
acute and chronic administration. Some similar actions
occur for natural rewards as well. Researchers are making
progress in understanding the molecular and cellular basis of
these common effects. A major goal for future research is to
determine whether such common underpinnings of addiction
can be exploited for the development of more effective
treatments for a wide range of addictive disorders.acute rewarding effects of all drug of abuse, and research over the past
several decades has delineated how each drug, regardless of its distinct
mechanism of action, converges on the VTA and NAc with common
acute functional effects (Fig. 1). Each drug activates dopaminergic
transmission in the NAc and many produce dopamine-like, yet dopamine-independent effects on the same NAc neurons, in many cases via
indirect, circuit-level actions18. In addition, several drugs (see Fig. 1
legend) seem to activate the brains endogenous opioid and cannabinoid systems within the VTA-NAc pathway, as exemplified by reduced
drug effects in cannabinoid and opioid receptor knockout mice, which
further underscores shared acute mechanisms of drug action1,8.On the basis of these common acute actions, one would expect
that chronic exposure to drugs of abuse would also cause common
chronic functional changes in the VTA-NAc pathway. Indeed, numerous common chronic adaptations have been described, examples of
which are discussed in the next sections. Consistent with common
mechanisms of addiction are the observations that certain drugs of
abuse, under particular experimental conditions, can induce crosstolerance and cross-sensitization to one another with respect to their
locomotor activating and rewarding effects9,10.More recent work has established that several additional brain areas
that interact with the VTA and NAc are also essential for acute drug
reward and chronic changes in reward associated with addiction.
These regions include the amygdala (and related structures of the socalled extended amygdala), hippocampus, hypothalamus and several
regions of frontal cortex, among others1,2,4,1013. Some of these areas
are part of the brains traditional memory systems; this has led to the
notion, now supported by increasing evidence, that important aspects
of addiction involve powerful emotional memories2,4,5,1113.Growing evidence...