Unmanageable Motivation in Addiction: A Pathology in Prefrontal-Accumbens Glutamate Transmission

  title={Unmanageable Motivation in Addiction: A Pathology in Prefrontal-Accumbens Glutamate Transmission},
  author={Peter W. Kalivas and Nora D. Volkow and Jeremy K. Seamans},

Figures from this paper

Neural mechanisms of addiction: the role of reward-related learning and memory.

Progress in identifying candidate mechanisms of addiction is reviewed, including molecular and cellular mechanisms that underlie long-term associative memories in several forebrain circuits (involving the ventral and dorsal striatum and prefrontal cortex) that receive input from midbrain dopamine neurons.

Exciting inhibition in psychostimulant addiction

Cocaine‐induced neuroadaptations in glutamate transmission

Preclinical studies of cocaine‐induced behavioral plasticity, including behavioral sensitization, self‐administration, and the reinstatement of cocaine seeking are focused on, as well as the progress and prospects of glutamate modulators for the treatment of cocaine addiction.

Chronic cocaine reduces RGS4 mRNA in rat prefrontal cortex and dorsal striatum

Re-exposure to the cocaine-associated context after abstinence renewed the drug seeking and restored the levels of RGS4 mRNA to control values, which might signal abnormal receptor G-protein coupling that impacts cocaine seeking.

Psychostimulant-induced neuroadaptations in nucleus accumbens AMPA receptor transmission.

Changes in AMPA receptor levels and subunit composition that occur after discontinuing different types of cocaine exposure, as well as changes elicited by cocaine reexposure following abstinence or extinction are reviewed.

Addiction as a pathology in prefrontal cortical regulation of corticostriatal habit circuitry

  • P. Kalivas
  • Psychology, Biology
    Neurotoxicity Research
  • 2009
It will be proposed that a transition between executive prefrontal cortical regulation of relapse to cortico-striatal habit circuitry can be modeled in animals trained to self-administer cocaine, and prefrontal regulation of the reinstatement of cocaine-seeking can be modeling by extinguishing the animals, thereby engaging cortical circuitry.

Prefrontal synaptic markers of cocaine addiction-like behavior in rats

Specific synaptic impairments in the prelimbic PFC (pPFC) circuits associated with addiction are identified and support the idea that alterations of synaptic plasticity are core markers of drug dependence.

Cocaine Interaction with Dopamine Transporter in the Prefrontal Cortex and Beyond

Although the relevant research investment in understanding the mechanism of action of cocaine and its role in altering brain circuits and behaviour has not been found yet, cocaine use, dependence, abuse and addiction are still a relevant health, social, and economical problem.

Neurobiology of cocaine addiction: implications for new pharmacotherapy.

  • P. Kalivas
  • Biology, Psychology
    The American journal on addictions
  • 2007
The development of pharmacotherapies for cocaine addiction has been disappointingly slow. However, new neurobiological knowledge of how the brain is changed by chronic pharmacological insult with



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.

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.

Cocaine Administered into the Medial Prefrontal Cortex Reinstates Cocaine-Seeking Behavior by Increasing AMPA Receptor-Mediated Glutamate Transmission in the Nucleus Accumbens

An animal model of cocaine relapse shows that AMPA and NMDA receptors in the nucleus accumbens have opposing roles in the reinstatement of cocaine-seeking behavior, and indicates that the glutamatergic pathway from the mPFC to the nucleus Accumbens plays an important role in cocaine priming-induced reinstate of drug seeking.

Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex.

An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed, and results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervalued of alternative rein forcers, and deficits in inhibitory control for drug responses.

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

Homer Proteins Regulate Sensitivity to Cocaine

Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli.

The data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.

Identification of PSD-95 as a Regulator of Dopamine-Mediated Synaptic and Behavioral Plasticity

Getting Formal with Dopamine and Reward