Enduring Effects of Chronic Ethanol in the CNS: Basis for Alcoholism

• Published in: Alcoholism, clinical and experimental research Vol. 27; no. 2; pp. 354 - 361
• Main Authors: Diana, Marco, Brodie, Mark, Muntoni, Annalisa, Puddu, Maria C., Pillolla, Giuliano, Steffensen, Scott, Spiga, Saturnino, Little, Hilary J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2003; Lippincott Williams & Wilkins
• Subjects: Abstinence; Alcohol Withdrawal Delirium - pathology; Alcohol Withdrawal Delirium - physiopathology; Alcohol-Induced Disorders, Nervous System - pathology; Alcohol-Induced Disorders, Nervous System - physiopathology; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Brain Damage, Chronic - pathology; Brain Damage, Chronic - physiopathology; Dopamine; Dopamine - physiology; Ethanol - toxicity; gamma-Aminobutyric Acid - physiology; Humans; Limbic System - pathology; Limbic System - physiopathology; Medical sciences; Mesencephalon - pathology; Mesencephalon - physiopathology; Mice; Mice, Inbred C57BL; Nerve Net - pathology; Nerve Net - physiopathology; Synaptic Transmission - drug effects; Toxicology; Ventral Tegmental Area - pathology; Ventral Tegmental Area - physiopathology; Ventral Tegmentum; Withdrawal; Poison withdrawal; Dopamine; Ethanol; Withdrawal; Alcoholism; Rodentia; Central nervous system; Electrophysiology; Abstinence; Gabaergic pathway; Vertebrata; Ventral Tegmentum; Mammalia; Mouse; Animal; Mesolimbic pathway; Dopaminergic pathway; Ventral tegmental area; Brain (vertebrata)
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1097/01.ALC.0000057121.36127.19

This symposium focused on functional alterations in the mesolimbic dopamine system during the abstinence phase after chronic alcohol intake. Mark Brodie first described his recordings from midbrain slices prepared after chronic alcohol treatment in vivo by daily injection in C57BL/6J mice. No changes were found in the baseline firing frequency of dopaminergic neurones in the VTA (ventral tegmental area), but the excitation produced in these neurones by an acute ethanol challenge was significantly increased in neurons from ethanol‐treated mice compared with those from the saline‐treated controls. There was also a significant decrease in the inhibitory response to GABA by the dopamine neurones following the chronic ethanol treatment. These data suggest that the timing pattern and mode of ethanol administration may determine the types of changes observed in dopaminergic reward area neurons. Annalisa Muntoni lectured on the relationship between electrophysiological and biochemical in vivo evidence supporting a reduction in tonic activity of dopamine neurons projecting to the nucleus accumbens at various times after suspension of chronic ethanol treatment and morphological changes affecting dopamine neurons in rat VTA. Hilary J. Little then described changes in dopaminergic neurone function in the VTA during the abstinence phase. Decreases in baseline firing were seen at 6 days after withdrawal of mice from chronic ethanol treatment but were not apparent after 2 months abstinence. Increases in the affinity of D1 receptors in the striatum, but not in the cerebral cortex, were seen however up to 2 months after withdrawal. Scott Steffensen then described his studies recording in vivo from GABA containing neurones in the VTA in freely moving rats. Chronic ethanol administration enhanced the baseline activity of these neurones and resulted in tolerance to the inhibition by ethanol of these neurones. His results demonstrated selective adaptive circuit responses within the VTA or in extrategmental structures that regulate VTA‐GABA neurone activity.