Acetaldehyde, motivation and stress: Behavioral evidence of an addictive ménage à trois
Front. Behav. Neurosci.. 2017-02-09; 11:
DOI: 10.3389/fnbeh.2017.00023
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Acetaldehyde (ACD) contributes to alcohol’s psychoactive effects through its own
rewarding properties. Recent studies shed light on the behavioral correlates of
ACD administration and the possible interactions with key neurotransmitters for
motivation, reward and stress-related response, such as dopamine and
endocannabinoids. This mini review article critically examines ACD psychoactive
properties, focusing on behavioral investigations able to unveil ACD motivational
effects and their pharmacological modulation in vivo. Similarly to alcohol, rats
spontaneously drink ACD, whose presence is detected in the brain following
chronic self-administration paradigm. ACD motivational properties are
demonstrated by operant paradigms tailored to model several drug-related
behaviors, such as induction and maintenance of operant self-administration,
extinction, relapse and punishment resistance. ACD-related addictive-like
behaviors are sensitive to pharmacological manipulations of dopamine and
endocannabinoid signaling. Interestingly, the ACD-dopamine-endocannabinoids
relationship also contributes to neuroplastic alterations of the NPYergic system,
a stress-related peptide critically involved in alcohol abuse. The understanding
of the ménage-a-trois among ACD, reward- and stress-related circuits holds
promising potential for the development of novel pharmacological approaches aimed
at reducing alcohol abuse.