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- W51427809 abstract "Significant progress has been made at every level of neuroscience research in understanding the mechanisms of action of drugs of abuse following both acute and chronic administration. The mechanism of action of drugs of abuse influence catecholamines at three levels of analysis: system, cellular, and molecular. At the system level, the focus on the mesolimbic dopamine system has led to the identification of neural circuits involved in drug reward and to a new concept of the extended amygdala. Dopamine elements of this extended amygdala, notably the shell or medial aspect of the nucleus accumbens, appear to be particularly sensitive to drug and natural rewards. Chronic stimulant administration leads to a progressive increase in stimulant-induced activity, and this sensitization is environment-dependent. At the cellular level, mesolimbic system dopamine neurons respond to chronic cocaine administration by increasing their activity while their activity decreases during withdrawal. At the level of the ventral tegmental area dopamine cell bodies, repeated administration of psychostimulants results in an inhibition of GABA release that contributes to the activation of mesolimbic neurons caused by increases in adenosine tone. Nucleus accumbens neurons show enhanced responsiveness to the inhibitory actions of D1 -receptor stimulation with repeated administration, and during withdrawal show a decreased responsiveness. At the molecular level, manipulations of specific neuropharmacological elements of dopaminergic neurotransrnission, such as knockout mice, are hypothesized to provide insights into the genetic vulnerability to substance dependence. The genetic basis for traits linked to substance dependence that are affected by multiple genes can be localized on the genome using quantitative trait loci analysis. These new genetic analyses and approaches, such as molecular genome manipulations and quantitative trait loci, provide hope for identifying elements that may confer vulnerability to substance abuse and dependence." @default.
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- W51427809 date "1997-01-01" @default.
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- W51427809 title "Drug Abuse and Alcoholism" @default.
- W51427809 doi "https://doi.org/10.1016/s1054-3589(08)60909-6" @default.
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