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The neural basis of addiction: a pathology of motivation and choice.
Cellular adaptations in prefrontal glutamatergic innervation of the accumbens promote the compulsive character of drug seeking in addicts by decreasing the value of natural rewards, diminishing cognitive control (choice), and enhancing glutamatorgic drive in response to drug-associated stimuli.
The Circuitry Mediating Cocaine-Induced Reinstatement of Drug-Seeking Behavior
Dopamine release in the dPFC initiates a dP FC–NAcore–VP series circuit that mediates cocaine-induced drug-seeking behavior, and is demonstrated to be specific to drug-related reinstatement.
The glutamate homeostasis hypothesis of addiction
  • P. Kalivas
  • Psychology, Biology
    Nature Reviews Neuroscience
  • 1 August 2009
The hierarchy of corticostriatal information processing that normally permits the prefrontal cortex to regulate reinforcement-seeking behaviours is impaired by chronic drug use and some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction.
Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies
The distinctions between drugs in the induction and expression of sensitization indicate that behavioral sensitization can arise from multiple neuroadaptations in multiple brain nuclei, not only the result of distinct molecular targets for the drugs, but may also include a differential involvement of learned associations.
Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse
Repeated cocaine treatment and withdrawal produces changes in brain function thought to be involved in relapse to drug use. Withdrawal from repeated cocaine reduced in vivo extracellular glutamate in
Prefrontal Glutamate Release into the Core of the Nucleus Accumbens Mediates Cocaine-Induced Reinstatement of Drug-Seeking Behavior
Together, these data demonstrate that activation of a glutamatergic projection from the prefrontal cortex to the nucleus accumbens underlies cocaine-primed reinstatement of drug-seeking behavior.
Extinction circuits for fear and addiction overlap in prefrontal cortex.
Given that the mPFC represents a common node in the extinction circuit for these behaviors, treatments that target this region may help alleviate symptoms of both anxiety and addictive disorders by enhancing extinction memory.
Limbic and Motor Circuitry Underlying Footshock-Induced Reinstatement of Cocaine-Seeking Behavior
The role of limbic, cortical, and striatal circuitry in a footshock reinstatement model of relapse to cocaine seeking was evaluated and suggested that footshock activates limbic circuitry in the CEA, which in turn activates a VTA dopamine projection to the PFCd.