Biphasic effects of alcohol on heart rate are influenced by alcoholic family history and rate of alcohol ingestion

The present study investigated cardiac response to acute alcohol challenge along the blood alcohol concentration (BAC) curve in two groups of young adult nonalcoholic men with (MFH) and without (FH-) multigenerational family histories of alcoholism, matched for drinking history. BACs and resting heart rate measurements were recorded every 10 min for 3 hr after ingestion of a 1.0 ml/kg dose of 95% USP alcohol at two different rates: one of 20 min (slow drinking) and the other of 5 min (fast drinking). Several analyses of variance were performed for each of the dependent measures [BAC and heart rate change from baseline (HRCH)]. A significant risk x BAC phase interaction emerged from the HRCH analysis, indicating that the MFH group was characterized by a significantly greater increase in resting heart rate along the ascending limb of the BAC curve. A significant risk x BAC phase x rate interaction indicated that, when alcohol was consumed at a faster rate, men with multigenerational family histories of alcoholism demonstrated a greater HRCH, which persisted throughout the BAC curve.     

Effects of alcohol on psychophysiological hyperreactivity to nonaversive and aversive stimuli in men at high risk for alcoholism.

Psychophysiological reactivity to nonaversive (1-KHz, 70-db tones) and aversive stimuli (shock) was examined in nonalcoholic men with multigenerational family histories (MFH) of alcoholism and family history negative (FH–) men, while sober and after consuming alcohol. In comparison with FH– Ss, sober MFH Ss had significantly larger skin conductance (SC) orienting responses (ORs), shorter OR latencies, slower habituation rates to the tones, and larger increases in heart rate and vasoconstriction to the shock. Alcohol dampened the magnitude of the SC-OR to the tones and the degree of cardiovascular reactivity to the shocks and increased the habituation rate to the tones in MFH Ss only. Alcohol consumption also increased the SC-OR recovery time in FH– Ss only. The MFH Ss' pattern of psychophysiological hyperreactivity is discussed in terms of a potential dysfunction in stimulus–response regulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential sensitivity to alcohol reinforcement in groups of men at risk for distinct alcoholism subtypes

The present study examines the relationship of familial and personality risk factors for alcoholism to individual differences in sensitivity to the positively and negatively reinforcing properties of alcohol. Sixteen sons of male alcoholics with multigenerational family histories of alcoholism (MFH) and 11 men who self-report heightened sensitivity to anxiety (HAS) were compared with 13 age-matched family history negative, low anxiety sensitive men (FH-LAS) on sober and alcohol-intoxicated response patterns. We were interested in the effects of alcohol on specific psychophysiological indices of "stimulus reactivity," anxiety, and incentive reward. Alcohol significantly dampened heart rate reactivity to aversive stimulation for the MFH and HAS men equally, yet did not for the FH-LAS group. HAS men evidenced idiosyncrasies with respect to alcohol-induced changes in electrodermal reactivity to aversive stimulation (an index of anxiety/fear-dampening), and MFH men demonstrated elevated alcohol-intoxicated resting heart rates (an index of psychostimulation) relative to the FH-LAS men. The results are interpreted as reflecting a sensitivity to the "stimulus reactivity-dampening" effects of alcohol in both high-risk groups, yet population-specific sensitivities to the fear-dampening and psychostimulant properties of alcohol in the HAS and MFH groups, respectively.     

Men at high risk for alcoholism: The effect of alcohol on cardiovascular response to unavoidable shock.

Three groups of 12 nonalcoholic men at differing degrees of genetic risk for alcoholism were tested with and without alcohol for their cardiovascular response to an aversive stimulus. A high-risk group consisted of sons of alcoholic fathers with extensive transgenerational family histories of alcoholism. A moderate-risk group included sons of alcoholic fathers whose previous generation was essentially negative for other alcoholic diagnoses. The low-risk group consisted of men with negative family histories for the disorder. Heart rate and digital blood volume amplitude were measured in each subject while resting and during a signaled shock procedure. Results show that the high-risk group was more cardiovascularly reactive to the stressor than the moderate-risk group when sober. Alcohol consumption led to a dramatic reduction in the degree of reactivity in the high-risk group, and it led to increased reactivity in the moderate-risk group. The trend for the low-risk group was similar to the moderate-risk group with no significant differences between the two. The methodology and results are discussed in terms of their relevance in the etiology of alcoholism in high-risk men and in terms of the need for generational controls in studying sons of alcoholics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alcohol challenge with sons of alcoholics: A critical review and analysis.

Studies are reviewed in which response to acute administration of alcohol was compared between individuals with and without family histories of alcoholism (FH+, FH–). This research represents a search for a psychobiological marker for alcoholism. A methodological critique of the procedures reported in this literature is then presented. Finally, a conceptual model is suggested in which differences in the response to alcohol between FH+ individuals and FH– individuals must be understood in relation to time after drinking alcohol. This Newtonian differentiator model proposes that sons of alcoholics exhibit acute sensitization as blood alcohol level rises and acute tolerance as blood alcohol level falls, compared with sons of nonalcoholics. Therefore, FH+ Ss find alcohol more rewarding because they accentuate the pleasurable, excitatory aspects of initial intoxication and attenuate the feelings of anxiety and depression that predominate as blood alcohol levels drop. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An heuristic model for the inherited predisposition to alcoholism.

Presents a research program for studying individuals genetically at high risk for alcoholism. Data from multigenerational nonproblem-drinking sons of male alcoholics indicate that the sons display a pattern of autonomic hyperreactivity to a variety of stimuli. This pattern of reactivity is significantly dampened by high doses of alcohol. These individuals also display difficulty on cognitive tests suggestive of prefrontal lobe dysfunction. This response pattern is not characteristic of controls nor of daughters of multigenerational male alcoholics. A model is presented that hypothesizes a cognitive disturbance underlying the hyperreactivity and posits a problem in the attribution of meaning to novel stimuli and threatening events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Searching for an environmental effect of parental alcoholism on offspring alcohol use disorder: A genetically informed study of children of alcoholics.

The children-of-twins design was used to isolate a potentially causal environmental impact of having an alcoholic parent on offspring alcohol use disorder, by an examination of whether the children of alcoholics were at a higher risk for alcohol use disorders than were the children of nonalcoholic parents, even after correlated familial factors were controlled. Participants were 1,224 male and female twins from 836 twin pairs selected from the Australian Twin Registry, 2,334 of the twins' 18-39-year-old offspring, and 983 spouses of the twins. Lifetime histories of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) alcohol use disorders were obtained by structured, psychiatric, telephone interviews conducted individually with each of the family members. Comparisons of the offspring of twins who were discordant for alcoholism indicated that there was no longer a statistically significant difference between the children of alcoholics and the children of nonalcoholics after genetic and family environmental factors correlated with having an alcoholic parent were controlled. The results of this study suggest that the direct causal effect of being exposed to an alcoholic parent on offspring alcohol use disorder is modest at best. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disulfiram for alcohol use disorders in adolescents

Alcohol abuse and dependence in adolescents is a serious health concern with significant morbidity and mortality. Disulfiram has been used to treat alcoholism in adults since 1948, but there are no known reports of disulfiram treatment in minors. Case reports are presented on the use of disulfiram in two adolescent males with alcohol dependence and strong family histories of alcoholism. Prolonged abstinence from alcohol occurred in the first case, whereas poor pharmacological compliance resulted in an early relapse in the second case. The judicious use of disulfiram in adolescents is recommended for consideration in those with alcohol use disorders. A protocol is proposed that recommends a thorough medical and psychiatric evaluation, documentation of a serious alcohol use disorder, careful assessment for comorbid diagnoses, family involvement when possible, and obtainment of informed consent that encompasses education about the nature and effects of disulfiram along with its potential interactions with other medications.     

Do adolescent symptomatology and family environment vary over time with fluctuations in paternal alcohol impairment?

This study tested whether adolescent internalizing problems, externalizing problems, heavy alcohol use, fathers' parenting, and family conflict varied over time with fluctuations in fathers' alcohol impairment and also whether children of recovered alcoholic fathers differed from children of nonalcoholic fathers. Fathers and adolescent children (N?=?267 families) were interviewed in 3 annual assessments. Results showed that adolescent symptomatology and the family environment did not vary over time as a function of different trajectories of paternal alcohol impairment. However, children of recovered alcoholic fathers exhibited more symptomatology than did children of nonalcoholic fathers. Even though paternal alcoholism has remitted in these families, children of recovered alcoholic fathers might remain on a general higher risk trajectory relative to children of nonalcoholic fathers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chronic alcohol use and age on human lymphocyte protein kinase C activity

The effects of alcohol exposure on human peripheral circulating lymphocyte protein kinase C (PKC) activity were characterized in lymphocytes harvested from two sample groups. The first group (control) consisted of 30 nonalcoholic male subjects and the second group consisted of nine male subjects with chronic alcoholism. Alcoholic subjects were admitted for detoxification to a substance abuse unit located in a nonprofit community hospital. In this group of subjects, blood was sampled on admission for detoxification (pre-A), and after 5 days (post-A). Subjects received chlordiazepoxide for treatment of alcohol withdrawal symptoms. PKC activities measured in the control, pre-A, and post-A groups expressed as pmol/microgram/min +/- SEM were 5.09 +/- 0.50, 1.81 +/- 0.43, and 3.95 +/- 0.44. Control PKC was significantly higher than pre-A PKC (p < or = 0.05) and post-A PKC was significantly higher than pre-A PKC (p < or = 0.05). Total lymphocyte PKC activity was also found to be inversely related to age, expressed by the relationship log(PKC) = 0.870-0.005(Age), with R = 0.433.     

Suppression of ethanol-reinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens

The opiate antagonist naltrexone suppresses ethanol-reinforced behavior in animals and decreases ethanol intake in humans. However, the mechanisms underlying these actions are not well understood. Experiments were designed to test the hypothesis that naltrexone attenuates the rewarding properties of ethanol by interfering with ethanol-induced stimulation of dopamine activity in the nucleus accumbens (NAcc). Simultaneous measures of the effects of naltrexone on dialysate dopamine levels in the NAcc and on operant responding for oral ethanol were used. Male Wistar rats were trained to self-administer ethanol (10-15%, w/v) in 0.2% (w/v) saccharin during daily 30 min sessions and were surgically prepared for intracranial microdialysis. Experiments began after reliable self-administration was established. Rats were injected with naltrexone (0.25 mg/kg, s.c.) or saline and 10 min later were placed inside the operant chamber for a 20 min waiting period with no ethanol available, followed by 30 min of access to ethanol. A transient rise in dialysate dopamine levels was observed during the waiting period, and this effect was not altered by naltrexone. Ethanol self-administration reliably increased dopamine levels in controls. Naltrexone significantly suppressed ethanol self-administration and prevented ethanol-induced increases in dialysate dopamine levels. Subsequent dose-effect analyses established that the latter effect was not merely a function of reduced ethanol intake but that naltrexone attenuated the efficacy of ethanol to elevate dialysate dopamine levels. These results suggest that suppression of ethanol self-administration by opiate antagonists is the result of interference with dopamine-dependent aspects of ethanol reinforcement, although possible additional effects via nondopaminergic mechanisms cannot be eliminated as a factor in opiate antagonist-induced reduction of ethanol intake.     

Risk for alcoholism and classical conditioning to signals for punishment: Evidence for a weak behavioral inhibition system.

Nonalcoholic men with high-density family histories of alcohol dependence (high risk) were compared with men with negative family histories (low risk) on a differential classical conditioning protocol that examined the acquisition of conditioned skin conductance responses (SCRs) to a tone (CS+) signaling the occurrence of an electric shock. High-risk Ss had significantly smaller SCRs to the CS+ tone probes during the acquisition phase and poor response discrimination between CS+ probes and CS– tones that were not paired with shock. The low-risk Ss showed a consistent pattern of discrimination between the CS+ and CS– tones. Unresponsivity to the CS+ probes was significantly related to more alcohol-related problems. The results suggest a relationship between risk for alcohol abuse and poor conditioning to signals for punishment, possibly reflecting weak behavioral inhibition system processes (D. C. Fowles; 1987). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ethanol-induced gastrointestinal damage. Influence of endogenous antioxidant components and gender

This study compared the effects of undiluted and 8% ethanol administered orally on gastrointestinal antioxidant components of male and female rats. Eight percent ethanol increased the activities of duodenal glutathione peroxide (29% in males, 14% in females) and superoxide dismutase in female gastric (24%) and male duodenal (15%) mucosa. This dose of ethanol also increased the glutathione content of gastric mucosa (12% in males, 13% in females). Undiluted ethanol decreased glutathione levels in gastric mucosa (22% in males, 11% in females) and increased glutathione peroxide activity in gastric mucosa (14% in males, 9% in females). Undiluted alcohol also produced decreases in the activity of glutathione reductase in stomach (14% in males, 9% in females) and duodenum (16% in males, 12% in females). Undiluted ethanol caused mucosal damage in the body of the stomach in both genders, accompanied by an increase in luminal pH and fluid accumulation in the stomach; these changes were absent in rats given 8% ethanol. The increase in gastrointestinal antioxidant capacity associated with the administration of 8% ethanol may be a factor in the reported cytoprotective effect of lower doses of ethanol.     

Brief report: Exaggerated ethanol-induced cardiac reactivity as an indicator of increased risk for gambling.

Pathological gambling and alcohol dependence show a high rate of co-occurrence. Some individuals at risk for alcohol dependence display an exaggerated heart rate (HR) increase following alcohol consumption, a characteristic suggesting sensitivity to reward. This study examined whether exaggerated ethanol-induced cardiac reactivity was associated with increased gambling behaviors. One hundred five young men (M = 20.13 years, SD = 1.07) consumed 1 ml of ethanol (95% volume) per kilogram of body weight. HR was measured and participants completed the South Oaks Gambling Screen (SOGS; H. R. Lesieur & S. B. Blume, 1987). Those with higher intoxicated HRs reported significantly greater scores on the SOGS (p = .02). This suggests that ethanol-induced HR increase is a possible marker for addictive disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Meta-analysis of P300 amplitude from males at risk for alcoholism.

The P3(00) event-related brain potential (ERP) is used to study the development of alcoholism by comparing males who have a positive family history of alcoholism with control Ss who have no such familial history. Meta-analysis indicated that overall, P3 amplitudes were obtained from males with family histories of alcoholism compared to controls. Moderator analysis indicated that paradigms using difficult visual tasks yielded the most reliable effects. Furthermore, no differences in outcomes were obtained among studies that recruited positive family history Ss exclusively from among individuals whose fathers had received treatment for alcoholism as compared with other studies. These findings are discussed in the context of using ERPs as an evaluative tool in the study of psychopathology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age differences in ethanol-induced hypothermia and impairment in mice

This experiment examined the effects of ethanol on body temperature and ethanol-induced impairment among three different age groups (8 months, 18 months, and 28 months) of C57BL/6NNIA male mice. Mice were injected intraperitoneally with 3 g/kg ethanol or an equivalent volume of saline. Body temperature, blood ethanol levels, and time when the righting response (RR) was lost and regained were measured. Body temperature also was measured prior to injection and at 30 and 120 min post-injection The aged mice showed less ethanol-induced hypothermia but were impaired longer as compared to the younger mice. Blood ethanol levels at loss and regaining of the RR were lower for old mice than the younger mice. Body temperature for the youngest group was lower at each time of measurement as compared to the older groups. Age differences in body temperature prior to ethanol or saline injection were small and nonsignificant.     

The glutamatergic basis of human alcoholism

OBJECTIVE: Although alcoholism is one of the most common psychiatric diagnoses, understanding of its pathophysiology remains poor. Accumulating evidence suggests that neurophysiological and pathological effects of ethanol are mediated to a considerable extent through the glutamatergic system. This article reviews the evidence of ethanol's effects on glutamatergic transmission and proposes a glutamatergic basis for alcoholism. METHOD: The information was derived from original research. The authors located more than 100 articles from psychiatry and neuroscience journals that related ethanol to glutamatergic transmission. They critically reviewed the neurobiology of the glutamatergic system in alcoholism and synthesized a unifying glutamatergic theory. RESULTS: Acute effects of ethanol disrupt glutamatergic neurotransmission by inhibiting the response of the N-methyl-D-aspartate (NMDA) receptor. Prolonged inhibition of the NMDA receptor by ethanol results in development of supersensitivity; acute removal of ethanol causes marked augmentation of activity of postsynaptic neurons, such as those in the noradrenergic system, and, in the extreme, glutamate-induced excitotoxicity. Neurobiological effects of alcoholism, such as intoxication, withdrawal seizures, delirium tremens, Wernicke-Korsakoff syndrome, and fetal alcohol syndrome, can be understood as a spectrum of consequences of ethanol's effect on the glutamatergic system. CONCLUSIONS: A host of findings support the hypothesis that the unifying mechanism of action of ethanol in interference with glutamatergic neurotransmission, especially through the NMDA receptor. Alcoholism may be considered another member of the expanding family of glutamate-related neuropsychiatric disorders. These insights should increase understanding of the biologic vulnerabilities leading to ethanol abuse and dependence and aid development of more effective pharmacologic interventions.     

Effects of alcohol abuse and familial alcoholism on physical health in men and women.

Administered a structured interview measuring 5 categories of physical health (medical history, alcohol-related disorders, trauma history, drug use history, and female-related disorders) to 76 male and 72 female detoxified alcoholics and 50 male and 51 female nonalcoholic controls. Ss were aged 21–62 yrs, and approximately half the Ss had a positive family history (FH) of alcoholism (AC). Results indicate that (1) alcoholics suffer pervasive physical health difficulties, (2) an FH of AC is predictive of health problems in both alcoholics and controls, (3) the effects of alcohol abuse and FH of AC on health are independent and additive, and (4) women may exhibit increased vulnerability to the adverse effects of AC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hormonal (ACTH, cortisol, beta-endorphin, and met-enkephalin) and cardiovascular responses to hyperthermic stress in chronic alcoholics

Chronic alcohol drinking causes profound alterations in hypothalamic-pituitary function. In the present study, endocrine [corticotropin (ACTH), beta-endorphin, cortisol, and met-enkephalin] and cardiovascular (blood pressure) changes in response to hyperthermic stress (sauna at 90 degrees C for 30 min) were evaluated in 25 normal men (25 to 50 years old) and in 48 male alcoholic subjects (34 to 56 years old) after 5 weeks of abstinence. Significantly lower increments in systolic blood pressure were observed in alcoholics than in control subjects. Furthermore, alcoholics showed lower ACTH, beta-endorphin, and cortisol increments in response to sauna than normal controls. In contrast, sauna-induced hyperthermia did not change significantly the circulating met-enkephalin levels in either normal controls or chronic alcoholics. These data suggest that an impairment in the adaptive response to stress affects alcoholic men even after a few weeks of abstinence from alcohol.     

Benzodiazepine receptor antagonists modulate the actions of ethanol in alcohol-preferring and -nonpreferring rats

The pyrazoloquinoline CGS 8216 (2-phenylpyrazolo-[4,3-c]-quinolin-3 (5H)-one, 0.05-2 mg/kg) and the beta-carboline ZK 93426 (ethyl-5-isopropyl-4-methyl-beta-carboline-3-carboxylate, 1-10 mg/kg) benzodiazepine receptor antagonists were evaluated for their capacity to modulate the behavioral actions of ethanol in alcohol preferring and -nonpreferring rats. When alcohol-preferring rats were presented with a two-bottle choice test between ethanol (10% v/v) and a saccharin (0.0125% g/v) solution, both antagonists dose-dependently reduced intake of ethanol by 35-92% of control levels on day 1 at the initial 15 min interval of the 4 h limited access. Saccharin drinking was suppressed only with the highest doses. CGS 8216 (0.25 mg/kg) and ZK 93426 (4 mg/kg) unmasked the anxiolytic effects of a hypnotic ethanol dose (1.5 g/kg ethanol) on the plus maze test in alcohol-preferring rats, but potentiated the ethanol-induced suppression in alcohol-nonpreferring rats. CGS 8216 (0.25 mg/kg) and ZK 93426 (4 mg/kg) attenuated the ethanol (0.5 and 1.5 g/kg)-induced suppression in the open field in alcohol-nonpreferring rats; however, CGS 8216 potentiated the depressant effects of the lower ethanol dose (0.5 g/kg) in alcohol-preferring rats. These findings provide evidence that benzodiazepine receptor antagonists may differentially modulate the behavioral actions of ethanol in alcohol-preferring and-nonpreferring rats. It is possible that the qualitative pharmacodynamic differences seen in the present study may be related to selective breeding for alcohol preference. The findings indicate the potential for development of receptor specific ligands devoid of toxic effects which may be useful in the treatment of alcohol abuse and alcoholism.