The neural basis of drug craving: An incentive-sensitization theory of addiction

http://umh1946.edu.umh.es/wp-content/uploads/sites/172/2015/04/Neurocircuitry-of-addiction1.pdf

Neurocircuitry of Addiction

LTP and LTD: an embarrassment of riches.

Drug addiction is increasingly viewed as the endpoint of a series of transitions from initial drug use--when a drug is voluntarily taken because it has reinforcing, often hedonic, effects--through loss of control over this behavior, such that it becomes habitual and ultimately compulsive. Here we discuss evidence that these transitions depend on interactions between pavlovian and instrumental learning processes. We hypothesize that the change from voluntary drug use to more habitual and compulsive drug use represents a transition at the neural level from prefrontal cortical to striatal control over drug seeking and drug taking behavior as well as a progression from ventral to more dorsal domains of the striatum, involving its dopaminergic innervation. These neural transitions may themselves depend on the neuroplasticity in both cortical and striatal structures that is induced by chronic self-administration of drugs.

/pdf/neural-systems-of-reinforcement-for-drug-addiction-from-3s2f74bu84.pdf

Neural systems of reinforcement for drug addiction: from actions to habits to compulsion

Over the past 20 years, neuroimaging has become a predominant technique in systems neuroscience. One might envisage that over the next 20 years the neuroimaging of distributed processing and connectivity will play a major role in disclosing the brain's functional architecture and operational principles. The inception of this journal has been foreshadowed by an ever-increasing number of publications on functional connectivity, causal modeling, connectomics, and multivariate analyses of distributed patterns of brain responses. I accepted the invitation to write this review with great pleasure and hope to celebrate and critique the achievements to date, while addressing the challenges ahead.

/pdf/functional-and-effective-connectivity-a-review-s5oik3vige.pdf

Functional and effective connectivity: a review.

The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants

The reinforcing (rewarding) effects of psychomotor stimulants (cocaine and amphetamine) depend on the mesocorticolimbic dopamine system innervating the nucleus accumbens ([Wise, 1981][1]; for review, see[Koob, 1992][2]), perhaps especially the shell subregion ([Bassareo and Di Chiara, 1997][3]).

http://www.neuroscience.ubc.ca/CourseMat/Everitt_Wolf_Addiction_review.pdf

Psychomotor Stimulant Addiction: A Neural Systems Perspective

The present invention provides a method for ameliorating cue-induced cravings for an addictive substance in abstinent addicts by administering a compound capable of blockade of GluR2-lacking AMPA receptors.

FORMATION OF ACCUMBENS GluR2-LACKING AMPA RECEPTORS MEDIATES INCUBATION OF COCAINE CRAVING

Regulation of AMPA receptor trafficking is important for many forms of neuronal plasticity. In this study, a protein cross-linking assay was used to evaluate the contribution of AMPA receptor trafficking to plasticity associated with behavioral sensitization, an animal model of drug addiction. Cross-linking was used to distinguish between cell surface and intracellular AMPA receptors in nucleus accumbens (NAc) tissue obtained from rats treated repeatedly with saline or cocaine. Surface/intracellular (S/I) ratios for glutamate receptor 1 (GluR1) and GluR2/3 subunits were increased 21 d after the last injection in cocaine-sensitized rats but not rats that failed to sensitize, and the magnitude of the S/I ratio for cocaine-sensitized rats was positively correlated with the magnitude of behavioral sensitization. At the 1 d withdrawal time, cocaine did not alter S/I ratios, and there was no correlation between S/I ratios and behavioral sensitization. The majority of surface-expressed GluR1 detected with this assay was associated with synapses, based on coimmunoprecipitation with postsynaptic density protein of 95 kDa. These findings suggest that behavioral sensitization to cocaine is associated with a slowly developing redistribution of AMPA receptors to the surface of NAc neurons. Motor execution of drug-seeking responses depends on activation of AMPA receptors on NAc neurons by glutamate afferents originating in cortical and limbic regions. We propose that drug-seeking responses are more effectively triggered in cocaine-sensitized rats because of increased cell surface expression of AMPA receptors.

https://www.jneurosci.org/content/jneuro/25/40/9144.full.pdf

Behavioral Sensitization to Cocaine Is Associated with Increased AMPA Receptor Surface Expression in the Nucleus Accumbens

Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here, I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and to further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction.

/pdf/synaptic-mechanisms-underlying-persistent-cocaine-craving-5a7erd0fql.pdf

Marina E. Wolf

Papers

The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants

Psychomotor Stimulant Addiction: A Neural Systems Perspective

FORMATION OF ACCUMBENS GluR2-LACKING AMPA RECEPTORS MEDIATES INCUBATION OF COCAINE CRAVING

Behavioral Sensitization to Cocaine Is Associated with Increased AMPA Receptor Surface Expression in the Nucleus Accumbens

Synaptic mechanisms underlying persistent cocaine craving