Trends in pharmacological sciences
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The fuel-sensing enzyme 5'-AMP-activated protein kinase (AMPK) has a major role in the regulation of cellular lipid and protein metabolism in response to stimuli such as exercise, changes in fuel availability and the adipocyte-derived hormones leptin and adiponectin. Recent studies indicate that abnormalities in cellular lipid metabolism are involved in the pathogenesis of the metabolic syndrome, possibly because of dysregulation of AMPK and malonyl-CoA, a closely related molecule. ⋯ Thus, it has been demonstrated recently that the tumor suppressor LKB1 is a kinase that has a major role in phosphorylating and activating AMPK, and that another tumor suppressor, tuberous sclerosis complex 2, is phosphorylated and activated by AMPK. In addition, other studies indicate that mammalian homolog of target of rapamycin (mTOR), which has been implicated in the pathogenesis of insulin resistance and many types of cancer, is inhibited by AMPK.
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Trends Pharmacol. Sci. · Feb 2005
ReviewWhy does the rapid delivery of drugs to the brain promote addiction?
It is widely accepted that the more rapidly drugs of abuse reach the brain the greater their potential for addiction. This might be one reason why cocaine and nicotine are more addictive when they are smoked than when they are administered by other routes. Traditionally, rapidly administered drugs are thought to be more addictive because they are more euphorigenic and/or more reinforcing. ⋯ We propose an alternative (although not mutually exclusive) explanation based on the idea that the transition to addiction involves drug-induced plasticity in mesocorticolimbic systems, changes that are manifested behaviourally as psychomotor and incentive sensitization. Recent evidence suggests that rapidly administered cocaine or nicotine preferentially engage mesocorticolimbic circuits, and more readily induce psychomotor sensitization. We conclude that rapidly delivered drugs might promote addiction by promoting forms of neurobehavioural plasticity that contribute to the compulsive pursuit of drugs.