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6.07.2.1 Opponent Motivational Process Hypothesis

The most intuitive explanation for addiction comes from the concept that drugs of abuse are initially taken for pleasure and that continued seeking of that pleasant effect leads to repeated exposure, which ultimately leads to neuroadaptations that cause tolerance, dependence, and unpleasant symptoms when the drug is absent. One prevailing view is that the mesolimbic dopaminergic system provides a 'reward circuit' which is stimulated through enhancement of intracellular DA levels in the NAc, either directly (e.g., cocaine and methamphetamine through indirect agonist actions), or indirectly through secondary stimulation of DA-release via opioidergic and cholinergic receptor agonist actions (e.g., opioids and nicotine).21 Chronic use of these drugs leads to disruption of homeostatic levels of many neurotransmitters including but not exclusively DA, and withdrawal produces a state of dysphoria18 leading to the cycle of addiction. Koob and colleagues have proposed that drug addiction is a result of dysregulation of the reward mechanism whereby a shift in positive reinforcement by the substance is replaced by negative reinforcement driving the behavior to

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