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.

  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · May 2014 · Addiction Biology
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Apr 2011 · Behavioural brain research
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Comorbid substance use in schizophrenic patients is common, and substance dependence is a predictive factor for psychosis. The present study was designed to investigate the effects of risperidone, quetiapine and ziprasidone, atypical antipsychotic drugs, on ethanol withdrawal syndrome (EWS) in rats. Adult male Wistar rats were used in the study. Ethanol (7.2%, v/v) was given to rats via a liquid diet for 21 days. An isocaloric liquid diet without ethanol was given to control rats. Risperidone (1 and 2 mg/kg), quetiapine (8 and 16 mg/kg), ziprasidone (0.5 and 1 mg/kg) and vehicle were injected into rats intraperitoneally at 1.5 and 5.5 h of ethanol withdrawal. At the 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, stereotyped behaviors, abnormal gait and posture, tail stiffness and agitation were recorded or rated. Following the observations at the 6th hour, the rats were tested for audiogenic seizures. All three drugs had some significant inhibitory effects on EWS-induced behavioral signs beginning at the 2nd hour of withdrawal. The drugs also significantly reduced the incidence of audiogenic seizures. Overall, risperidone and quetiapine seemed to be more effective than ziprasidone in ameliorating the withdrawal signs. Doses of the drugs used in the present study did not produce any significant changes in locomotor activities of naïve rats. Our results suggest that risperidone, quetiapine and ziprasidone had beneficial effects on EWS in rats. Thus, these drugs may be helpful for controlling withdrawal signs in ethanol-dependent patients.
    Full-text · Article · Dec 2010 · Progress in Neuro-Psychopharmacology and Biological Psychiatry
Show more