Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia

Department of Psychiatry, Columbia University, New York, New York, United States
Neuropsychopharmacology (Impact Factor: 7.05). 01/2007; 31(12):2767-75. DOI: 10.1038/sj.npp.1301207
Source: PubMed


The purpose of this study was to determine whether schizophrenia was associated with alterations in alcohol response that might explain the elevated risk for AUDs in this population. In a randomized, double-blind, placebo-controlled, counter-balanced 3 test day laboratory study, the effects of alcohol were compared in 23 subjects with schizophrenia (without any previous alcohol use disorder (AUD) but with some alcohol exposure) and in 14 healthy subjects matched for age, gender, education, and lifetime exposure to alcohol. Standard alcohol drinks in a scheduled design were administered to produce blood alcohol levels of 0, 0.02-0.04 mg%, or 0.06-0.08 mg%. Schizophrenia symptoms, perceptual alterations, stimulant and depressant subjective effects of alcohol, and 'high' were measured before alcohol administration and at several post-drug time points. Verbal learning and recall, vigilance and distractibility, and motor function were assessed once per test day. Relative to healthy subjects, subjects with schizophrenia reported greater euphoria and stimulatory effects in response to alcohol. Alcohol produced small transient increases in positive psychotic symptoms and perceptual alterations without affecting negative symptoms. Alcohol also impaired several aspects of immediate and delayed recall, and vigilance, and distractibility. Schizophrenia patients showed increased euphoric and stimulatory responses to alcohol. These exaggerated positive responses to alcohol doses may contribute to the increased risk for AUDs associated with schizophrenia. The absence of 'beneficial' effects of alcohol does not support a self-medication hypothesis of alcohol use in schizophrenia.

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Available from: Tahir Tellioglu, Apr 15, 2014
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    • "In this model, some studies revealed addictive-like behaviors, mainly by using cocaine (Chambers & Taylor 2004; Chambers, Sheehan & Taylor 2004; Chambers et al. 2010a; Chambers, Sentir & Engleman 2010b), amphetamines and (Brady et al. 2008) nicotine (Berg & Chambers 2008; Berg et al. 2013) but rarely by alcohol. These latter studies revealed that neonatal ventral hippocampal lesion (NVHL) rats exhibit higher ethanol (EtOH)-induced sensitization (Conroy, Rodd & Chambers 2007), which can be compared with the enhanced alcohol-induced euphoria seen in human SCZ (D'Souza et al. 2006). The same group recently showed that NVHL rats consume more alcohol in a two-bottle choice paradigm (Berg, Czachowski & Chambers 2011). "
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    ABSTRACT: Schizophrenia is a mental disorder characterized by a series of positive, negative or cognitive symptoms but with also the particularity of exhibiting a high rate of co-morbid use of drugs of abuse. While more than 80% of schizophrenics are smokers, the second most consumed drug is alcohol, with dramatic consequences on frequency and intensity of psychotic episodes and on life expectancy. Here we investigated the impact of light alcohol intake during adolescence on the subsequent occurrence of alcohol addiction-like behavior in neonatal ventral hippocampal lesion (NVHL) rats, a neurodevelopmental model of schizophrenia. Our findings demonstrated an increased liability to addictive behaviors in adult NVHL rats after voluntary alcohol intake during adolescence. NVHL rats displayed several signs of alcohol use disorder such as a loss of control over alcohol intake and high motivation to consume alcohol, associated with a higher resistance to extinction. In addition, once NVHL rats relapsed, they maintained higher drinking levels than controls. We finally showed that the anti-addictive drug naltrexone is efficient in reducing excessive alcohol intake in NVHL rats. Our results are in accordance with epidemiological studies underlying the particular vulnerability to alcohol addiction after adolescent exposure to alcohol and highlight the fact that schizophrenic subjects may be particularly at risk even after light alcohol consumption. Based on these results, it seems particularly relevant to prevent early onset of alcohol use in at-risk subjects and thus to reduce the incidence of co-morbid alcohol abuse in psychotic patients.
    Addiction Biology 05/2014; 20(3). DOI:10.1111/adb.12146 · 5.36 Impact Factor
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    • "Neurodevelopmental abnormalities involving these systems in NVHLs may be particularly sensitive to the reinforcing effects of ethanol when sucrose is present, as suggested by our findings. While the euphoric effects of ethanol may be a subjective correlate of the positive reinforcing effects of ethanol [21], the euphoric effects of ethanol have been shown to be enhanced in schizophrenia when patients are given a carbohydrate/ethanol solution [22]. "
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    ABSTRACT: Alcohol abuse in schizophrenia exceeds rates in the general population and worsens illness outcomes. Neonatal ventral hippocampal lesion (NVHL) rats model multiple schizophrenia dimensions including addiction vulnerability. This study compared NVHL vs. SHAM-controls in operant alcohol seeking and consumption. NVHLs enhanced consumption of combined ethanol/sucrose solution but neither ethanol or sucrose only solutions, consistent with increased vulnerability specific to carbohydrate-laden alcohol beverages typically consumed in early stages of human alcoholism.
    Behavioural brain research 04/2011; 218(2):346-9. DOI:10.1016/j.bbr.2010.12.017 · 3.03 Impact Factor
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    • "Both dopaminergic and serotonergic systems play a crucial role in the development of ethanol dependence (Kuriyama and Ohkuma, 1990; Uzbay, 2008), and recent reports indicate that there is a relationship between schizophrenia and ethanol dependence (D'Souza et al., 2006; Seeman et al., 2006; Conroy et al., 2007). There may be potential beneficial effects of new atypical antipsychotic drugs in the treatment of the signs of ethanol withdrawal as well as blocking the craving effects of ethanol (Drake et al., 2000; Hutchison et al., 2003). "
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