Elsevier

Alcohol

Volume 2, Issue 2, March–April 1985, Pages 367-370
Alcohol

A multi-demensional examination of the positive reinforcing properties of acetaldehyde

https://doi.org/10.1016/0741-8329(85)90077-1Get rights and content

Abstract

The suggestion that acetaldehyde may be endowed with positive reinforcing properties and may in fact mediate some of the psychopharmacological actions of ethanol has been examined by us and other investigators using a variety of paradigms. We first reported that non-dependent animals would self-administer acetaldehyde through an intra-cerebroventricular route. In addition, we have demonstrated that central infusion induced a conditioned place preference. We have also shown that an animal's propensity to self-administer acetaldehyde directly into the brain was related to its subsequent voluntary intake of ethanol. Lastly, we have reported that inhibition of acetaldehyde metabolism resulted in an enhancement of alcohol-induced euphoria in man. The data collected to date from four different paradigms strongly support the notion that acetaldehyde is endowed with positive reinforcing properties which may play a critical role in the mediation of ethanol euphoria.

References (39)

  • B.R. Smith et al.

    Conditioned place preference induced by intraventricular infusions of acetaldehyde

    Alcohol

    (1984)
  • S. Socaransky et al.

    Brain ALDH as a possible modulator of voluntary ethanol intake

    Alcohol

    (1985)
  • J.Y. Westcott et al.

    In vivo acetaldehyde in the brain of rat treated with ethanol

    Biochem Pharmacol

    (1980)
  • J. Akabane

    Aldehydes and related compounds

  • S. Amir et al.

    The role of acetaldehyde in the psychopharmacological effects of ethanol

  • Z. Amit et al.

    A further investigation of alcohol preference in the laboratory rat induced by hypothalamic stimulation

    Psychopharmacology

    (1971)
  • D. Behar et al.

    Behavioral and physiological effects of ethanol in high-risk and control children: A pilot study

    Alcohol: Clin Exp Res

    (1983)
  • Z.W. Brown et al.

    Intraventricular self-administration of acetaldehyde but not ethanol in naive laboratory rats

    Psychopharmacology (Berlin)

    (1979)
  • Z.W. Brown et al.

    Alcohol-induced euphoria enhanced by disulfiram and calcium carbimide

    Alcohol: Clin Exp Res

    (1983)
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