Credible evidence also implicates serotonergic, opioid, endocannabinoid, GABAergic and glutamatergic mechanisms in addiction. Neuroimaging studies in humans add credence to this hypothesis. Addiction appears to correlate with a hypodopaminergic dysfunctional state within the reward circuitry of the brain. In short, the 'bio-psycho-social' model of etiology holds very well for addiction. There are important genetic variations in vulnerability to drug addiction, yet environmental factors such as stress and social defeat also alter brain-reward mechanisms in such a manner as to impart vulnerability to addiction. The brain circuits mediating the pleasurable effects of addictive drugs are anatomically, neurophysiologically and neurochemically different from those mediating physical dependence, and from those mediating craving and relapse.
Postuse dysphoria then comes to dominate reward circuit hedonic tone, and addicts no longer use drugs to get high, but simply to get back to normal ('get straight'). opiates), tolerance to the euphoric effects develops with chronic use. For some classes of addictive drugs (e.g. Drug self-administration is regulated by nucleus accumbens dopamine levels, and is done to keep nucleus accumbens dopamine within a specific elevated range (to maintain a desired hedonic level). All addictive drugs have in common that they enhance (directly or indirectly or even transsynaptically) dop-aminergic reward synaptic function in the nucleus accumbens. The 'second-stage' dopaminergic component in this reward circuitry is the crucial addictive-drug-sensitive component. 'Hedonic dysregulation' within these circuits may lead to addiction. Although originally believed to simply encode the set point of hedonic tone, these circuits are now believed to be functionally far more complex, also encoding attention, expectancy of reward, disconfirmation of reward expectancy, and incentive motivation. The core reward circuitry consists of an 'in-series' circuit linking the ventral tegmental area, nucleus accumbens and ventral pallidum via the medial forebrain bundle. Addictive drugs have in common that they are voluntarily self-administered by laboratory animals (usually avidly), and that they enhance the functioning of the reward circuitry of the brain (producing the 'high' that the drug user seeks).
0 kommentar(er)
