Unbound MEDLINE

Stress history increases alcohol intake in relapse: relation to phosphodiesterase 10A.

Abstract

Stressful experiences can result in elevated alcohol drinking, as exemplified in many individuals with post-traumatic stress disorder. However, how stress history, rather than acute stressors, influences alcohol intake remains uncertain. To model the protracted effects of past stress, male Wistar rats were subjected to light-cued footshock (stress history) or light cues alone (control) prior to acquisition of alcohol self-administration (1-hour sessions, fixed ratio 1-3, 100 µl of 10% v/v alcohol as reinforcer). Stress history did not alter mean alcohol intake during acquisition of self-administration, but it increased preference for the alcohol-paired lever over the inactive lever. Following an extinction period, rats with a history of stress exposure and low baseline alcohol intake showed a twofold elevation in alcohol self-administration, as compared with low-drinking rats with no stress history. Similar effects were not seen in rats self-administering 0.1% sucrose. Analysis of mRNA levels of phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate and cyclic guanosine monophosphate hydrolyzing enzyme, showed that stress history increased Pde10a mRNA levels in the basolateral amygdala and, in low-drinking rats, the prelimbic prefrontal cortex (plPFC). Pde10a mRNA levels in the plPFC correlated directly with greater alcohol self-administration during the relapse-like phase, and greater BLA Pde10a mRNA levels correlated with increased ethanol preference after acquisition. The data demonstrate that stress history sensitizes otherwise low alcohol drinkers to consume more alcohol in a relapse-like situation and identify stress-induced neuroadaptations in amygdala and prefrontal cortical Pde10a expression as changes that may drive heightened alcohol intake and preference in susceptible individuals.

Links

  • PMC Free PDF
  • Publisher Full Text
  • Authors

    Logrip ML, Zorrilla EP

    Institution

    Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.

    Source

    Addiction biology 17:5 2012 Sep pg 920-33

    MeSH

    Alcoholism
    Amygdala
    Analysis of Variance
    Animals
    Central Nervous System Depressants
    Conditioning, Operant
    Ethanol
    Extinction, Psychological
    Male
    Phosphoric Diester Hydrolases
    Photic Stimulation
    Prefrontal Cortex
    Rats
    Rats, Wistar
    Recurrence
    Stress, Psychological

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    22741603