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

Neurocircuitry of Addiction

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

https://sites.oxy.edu/clint/physio/article/therewardcircuitlinkingprimateanatomyandhumanimaging.pdf

The reward circuit: linking primate anatomy and human imaging.

Addiction is a state of compulsive drug use; despite treatment and other attempts to control drug taking, addiction tends to persist. Clinical and laboratory observations have converged on the hypothesis that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. The major substrates of persistent compulsive drug use are hypothesized to be 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. Here we review progress in identifying candidate mechanisms of addiction.

https://www.ausl.fe.it/azienda/dipartimenti/daismdp/staff/osservatorio-epidemiologico/documenti-scaricabili/convegni/corso-di-formazione-aggiornamento-di-farmacoterapia-in-uso-al-sert/3-himan-mecc-dipendenza/at_download/file

NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory

The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.

Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications

Although the voluntary intake of drugs of abuse is a behavior largely preserved throughout phylogeny, it is currently unclear whether pathological drug use (“addiction”) can be observed in species other than humans. Here, we report that behaviors that resemble three of the essential diagnostic criteria for addiction appear over time in rats trained to self-administer cocaine. As in humans, this addiction-like behavior is present only in a small proportion of subjects using cocaine and is highly predictive of relapse after withdrawal. These findings provide a new basis for developing a true understanding and treatment of addiction.

https://science.sciencemag.org/content/sci/305/5686/1014.full.pdf

Evidence for addiction-like behavior in the rat.

Both impulsivity and novelty-seeking have been suggested to be behavioral markers of the propensity to take addictive drugs. However, their relevance for the vulnerability to compulsively seek and take drugs, which is a hallmark feature of addiction, is unknown. We report here that, whereas high reactivity to novelty predicts the propensity to initiate cocaine self-administration, high impulsivity predicts the development of addiction-like behavior in rats, including persistent or compulsive drug-taking in the face of aversive outcomes. This study shows experimental evidence that a shift from impulsivity to compulsivity occurs during the development of addictive behavior, which provides insights into the genesis and neural mechanisms of drug addiction.

https://science.sciencemag.org/content/sci/320/5881/1352.full.pdf

High Impulsivity Predicts the Switch to Compulsive Cocaine-Taking

We hypothesize that drug addiction can be viewed as the endpoint of a series of transitions from initial voluntary drug use through the loss of control over this behaviour, such that it becomes habitual and ultimately compulsive. We describe evidence that the switch from controlled to compulsive drug seeking represents a transition at the neural level from prefrontal cortical to striatal control over drug-seeking and drug-taking behaviours as well as a progression from ventral to more dorsal domains of the striatum, mediated by its serially interconnecting dopaminergic circuitry. These neural transitions depend upon the neuroplasticity induced by chronic self-administration of drugs in both cortical and striatal structures, including long-lasting changes that are the consequence of toxic drug effects. We further summarize evidence showing that impulsivity, a spontaneously occurring behavioural tendency in outbred rats that is associated with low dopamine D2/3 receptors in the nucleus accumbens, predicts both the propensity to escalate cocaine intake and the switch to compulsive drug seeking and addiction.

/pdf/neural-mechanisms-underlying-the-vulnerability-to-develop-2yf8uvlnah.pdf

Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction

https://www.cell.com/neuron/pdf/S0896-6273(07)01032-X.pdf

David Belin

Papers

Evidence for addiction-like behavior in the rat.

High Impulsivity Predicts the Switch to Compulsive Cocaine-Taking

Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction

Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum.

Parallel and interactive learning processes within the basal ganglia: relevance for the understanding of addiction.