Molecular Pathways Involved in Drug Abuse and Their Implication in Impulsivity and Learning Processes

Dear colleagues,

Drugs of abuse have very different acute mechanisms of action, but all converge in the same circuitry in the brain’s limbic system, yielding a set of common functional effects, especially after chronic administration.

The main problem in the treatment of addiction is that, after repeated exposure to the reinforcer, several brain circuitry adaptations have occurred and drug-seeking behaviors have turned into a compulsive use. A wide and diverse body of evidence has pointed out these adaptations as the main contributors to intense drug craving and relapse, often triggered by drug-associated cues, which can persist even after long periods of abstinence. Molecular and cellular mechanisms that underlie long-term associative memories have been implicated in persistent compulsive drug use.

The mesolimbic dopamine pathway, including dopaminergic neurons in the ventral tegmental area and their targets in the limbic system, especially the nucleus accumbens, is one of the most important substrates for the acute rewarding effects of all drugs of abuse. Drugs of abuse activate dopaminergic transmission in the nucleus accumbens, either directly or indirectly. Dopamine release is implicated in the development of memory that links the motivational effects of the drug to neutral environmental cues, in such a way that now drug addiction is considered a disease of learning, a pathological colonization of the neural mechanisms of the learning process.

In the brain cortex, the frontal lobes manage behavioral control through executive functions, such as inhibition of impulsive responses and of aggressive behavior. Dysfunctional impulsivity includes deficits in attention, lack of reflection, and a plethora of traits, all of which emerge in drug addiction. In this regard, impulsivity is a risk factor for drug experimentation and problematic drug use, but also a consequence of this misuse. The present Special Issue is focused on establishing the basis for studying the neurobiological substrates of impulsivity.

This Special Issue of Biomolecules presents several papers and review articles focused on molecular mechanisms underlying long-term associative memories in drug abuse, but also encourages the studies of cellular pathways that are involved in the changes to executive functions accompanying addictive phenomena.

Prof. Elena Escubedo
Prof. David Pubill
Guest Editors

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• dysfunctional impulsivity
• learning
• associative memory
• drug abuse
• compulsive use
• dopamine circuitry