THE PHYSIOLOGICAL AND BEHAVIOURAL EFFECTS OF MODERATE DOSES OF ALCOHOL: The Psychopharmacology of Social Drinking

Feelings of intoxication induced by alcohol are biphasic. Atlow doses alcohol produces excitation—intoxication andat high doses C.N.S. depression. It is suggested that normal social drinkers drink to facilitateexcitation—intoxication, a technique either never acquiredor for other new reasons worse than useless for alcoholics.The possible application of this suggested treatment is discussed. If it is desired to return alcoholics to normal social drinking,a great deal more needs to be known about bodily responses toalcohol both in the normal and the abnormal drinker.     

Dependence on legal psychotropic drugs among alcoholics

Aims: Dependence on legal psychotropic drugs (PTD) has beenreported to have increased in alcoholics, but previous studiesreport conflicting results concerning the rate of increase andclinical characteristics. The aim of the present study was first,to assess the dependence rate of PTD among alcoholics in openand institutionalized care, and to compare these populationswith the general population, and second, to assess rates anddoses of high- and low-dose PTD-dependence among alcoholics.Methods: In 1997, alcoholics in open and institutionalized carewere asked to anonymously fill in a questionnaire on their druguse and dependence. Healthy controls were included. The numberof attending subjects was 130 open-care alcoholics at the Departmentof Alcohol and Drug Diseases in Malmö, Sweden; 23 alcoholicsin institutionalized care at Karlsvik Rehabilitation Centrein Höör, Sweden; and 120 healthy controls at VårdcentralenKirseberg, a primary health care centre located in a Malmöarea. The approximate attendance rate was 75, 70 and 95%, respectively.The questionnaire was based on DSM-IV criteria for dependence.Results: The total rate of PTD-dependent alcoholics was higherin the institutionalized group (35%) than in the open-care setting(14%): difference in proportions (p₁–p₂ 21%; 95% CI: 1%,41%). Alcoholics were more often PTD-dependent (17%) than werehealthy controls (2%), (p₁–p₂ 15%; 95% CI: 9%, 21%). Benzodiazepines(BZD) were the most common PTD. Only four out of a total of23 BZD-dependent alcoholics developed high-dose BZD-dependence.Those subjects were also misusing other drugs, including cannabis.Conclusions: We conclude that alcoholism is associated withlegal PTD-dependence and illegal drug misuse. High-dose BZD-dependenceis infrequent among BZD-dependent alcoholics.     

Morphine influence on adenylate cyclase activity in peripheral blood lymphocytes of alcoholic patients.

The effect of morphine on adenylate cyclase activity in lymphocytes was tested in 20 normal controls, 16 alcoholics in withdrawal and 9 sober alcoholics. Alcoholics in withdrawal were characterized by a significantly increased stimulatory effect of morphine, whereas sober alcoholics showed an inhibitory effect. The morphine effect was abolished by naloxone and correlated with the severity of withdrawal and alcohol intoxication.     

Effects of aspirin on gastroduodenal permeability in alcoholics and controls

Alcohol and nonsteroidal anti-inflammatory drugs are noxious agents that can disrupt the integrity of the gastroduodenal mucosal and damage the epithelial barrier and lead to increased gastroduodenal permeability. Moreover, it is not uncommon that patients are exposed to these two barrier stressors at the same time. It is thus important to know how simultaneous exposure affects the gastroduodenal barrier, and acquiring that knowledge was the goal of this study. We used a method that has been widely used for the assessment of injury to the gastroduodenal barrier induced by these noxious agents—measurement of gastroduodenal permeability as indicated by urinary excretion of ingested sucrose. We used gas chromatography to measure the amount of sucrose excreted in the urine over the 5-12 h after ingestion of a bolus of sucrose. The 148 participants in the study included 92 alcoholics and 56 healthy controls. All study subjects had a baseline permeability test. To determine whether addition of a second noxious agent, in addition to chronic alcohol, further decreases gastroduodenal barrier integrity, a subset of 118 study subjects participated in another permeability test in which they were exposed to aspirin. For this test, participants ingested 1,300 mg aspirin twice, 12 and 1 h before the final permeability test. The baseline permeability test showed that alcoholics have significantly higher gastroduodenal permeability than controls. Aspirin caused a significant within-group absolute increase in gastroduodenal permeability in both alcoholics and controls (+7.72%, P = .003 and +2.25%, P = .011, respectively), but the magnitude of these increases was not significantly different from each other. Baseline permeability did vary by gender, self-reported illegal drug use, and employment type. The extent of the permeability increase after aspirin ingestion varied with illegal drug use and recruitment site (a surrogate marker of socioeconomic status). Our data show that alcoholics have greater gastroduodenal permeability than healthy controls. This difference was independent of the duration of any preceding period of sobriety, gender, smoking history, or illicit drug abuse. The injurious effects of alcohol on the gastroduodenal epithelial barrier are long lasting, persisting even after 7 days of sobriety. Although, acute aspirin and chronic alcohol each increase intestinal permeability in alcoholics, their effects appear to be additive rather than synergistic.     

Characteristics of receptors and enzymes in brains of human alcoholics

Acute and chronic ethanol administration to animals has been shown to produce changes in the turnover of numerous neurotransmitters, as well as to change the characteristics of certain neurotransmitter receptors. In the present study, brains obtained from human alcoholics and matched control subjects were examined for similar changes. In frontal cortex, the affinity of opiate receptors for dihydromorphine was significantly reduced in brains of alcoholics. Judging from animal studies, this change may reflect alterations in opiate receptor-effector coupling processes. No changes were observed in muscarinic cholinergic or beta-adrenergic receptors in humans, in contrast to animals, possibly because of the protracted abstention from alcohol among the alcoholic patients prior to death. Similarly, no changes in the activities of choline acetyltransferase, tyrosine hydroxylase or MAO-B were observed in brains of alcoholics as compared to the control population. Our studies suggest that many of the alterations witnessed during alcohol intoxication and withdrawal in animals may be more subtle in humans, or may be reversible with abstinence.     

Evaluation of plasma cholesteryl ester transfer protein (CETP) activity as a marker of alcoholism.

Plasma cholesteryl ester transfer protein (CETP) activity was measured in 52 alcoholics and 38 controls and compared with conventional laboratory markers of alcoholism. Mean daily alcohol intake was 180 g/day among the alcoholics and 10 g/day among the controls. Plasma CETP activity was 26% lower in the alcoholics (P < 0.001) and was inversely correlated with daily alcohol intake (r = -0.288, P < 0.05). CETP activity detected 63% of the alcoholics, and its specificity was 82% if the cut-off point was set at the mean CETP activity of the controls -1 SD. The mean -2 SD gave a very low sensitivity for CETP (8%) and cannot be used as its cut-off point. The sensitivities and specificities of gamma glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, mean corpuscular volume and high-density lipoprotein cholesterol were similar to those of CETP activity when the cut-off point for CETP was mean -1 SD. The results thus indicate that plasma CETP activity is not sufficient as a single marker of alcoholism but could be used as an additional method to detect alcohol misuse, although its wide variation in normal population and the elaborate analysis limit its usefulness.     

Influence of mouse genotype on responses of central cholinergic neurotransmission to long term alcohol intoxication

Cholinergic neurotransmission has been followed in striatum and hippocampus in two inbred strains of mice (C57Bl/6 and Balb/c) during long term alcohol exposure (over a 25 month period) and with aging. Marked strain dependent differences in reactivity of pre- and postsynaptic cholinergic markers to chronic alcohol exposure and aging were demonstrated in both structures. The Balb/c strain exhibits a remarkable long lasting tolerance to alcohol injury for striatal and hippocampal cholinergic markers (choline acetyltransferase, high affinity choline uptake, muscarinic receptors affinity, acetyl cholinesterase), whereas C57Bl mice appear more sensitive to alcohol intoxication. Likewise aging affects the C57Bl mouse more severely than the Balb/c, a phenomenon which may be involved in the sensitivity of these mice to alcohol intoxication. Moreover long term alcohol exposure, in addition to aging show unequal effects on the diverse cholinergic markers studied. Also divergences of specific brain areas have been noted and should be related to their particular neuroanatomy. Such discrepancies may, in part, explain differences observed in the behavioral effects of chronic alcohol intoxication in alcoholics.     

A Comparative Study of Mortality Among Puerto Rican Injection Drug Users in East Harlem, New York, and Bayamon, Puerto Rico

Drug users have been found to be at high risk of mortality but the mortality experience of Hispanic drug users remains understudied. This study assessed mortality among Puerto Rican injection drug users (IDUs) in New York City (NY), and in Puerto Rico (PR). Study subjects were 637 IDUs from NY and 319 IDUs from PR. Mortality was ascertained using data from the National Death Index. Annual mortality rate of the NY cohort was 1.3 per 100 person years compared to the PR cohort with a rate of 4.8. Compared to the Hispanic population of New York City, the standardized mortality ratio (SMR) of the NY cohort was 4.4. Compared to the population of Puerto Rico, the SMR of the PR cohort was 16.2. The four principal causes of death were: NY—HIV/AIDS (50.0%), drug overdoses (13.3%), cardiovascular conditions (13.3%), and pulmonary conditions (10.0%); PR—HIV/AIDS (37.0%), drug overdoses (24.1%), sepsis (13.0%), and homicide (11.1%). Modeling time to death using Cox proportional hazards regression, the relative risk of mortality of the PR cohort as compared to the NY cohort was 9.2. The other covariates found to be significantly associated with time to death were age, gender, education, social isolation, intoxication with alcohol, and HIV seropositivity. The large disparity in mortality rates found in this study suggests that health disparities research should be expanded to identify intra-group disparities. Furthermore, these results point to an urgent need to reduce excess mortality among IDUs in Puerto Rico.     

ALCOHOLISM MORTALITY RATE IN JAPAN

The death rates due to alcoholism in Japan were analysed forthe period 1950–1978. The alcoholism death rates for bothsexes increased each year. The alcoholism death rates were closelyrelated to the levels of alcohol consumption. Among both sexes the lowest age-adjusted death rates were observedin married persons and the highest death rates in divorced persons. Geographical variations in the alcoholism death rates were analysed;they were also correlated with alcohol consumption levels. Themean ages at death for alcoholics were 50 for men and 48 forwomen; the mean ages remained constant during the period ofstudy.     

Drinking pattern and alcohol-related medical disorders.

Although heavy alcohol intake is known to be one of the most common causative factors of liver disease, pancreatitis, upper gastrointestinal and neurological disorders, the influence of the drinking pattern is largely unknown. The study investigated the relationship of alcohol-related medical disorders in alcoholics and their drinking pattern. Two hundred and forty-one chronic alcoholics were referred consecutively for detoxification and their drinking pattern was sufficient for them to be included in this study. History of alcohol abuse as well as drinking behaviour in the last 6 months were assessed by a semi-structured interview. Findings included intensive clinical examination with abdominal ultrasound in most subjects. Heavy drinking with frequent inebriation was most often found in our sample (44.4%), whereas continuous heavy alcohol consumption without intoxication (33.6%), and an episodic drinking style (22.0%) were less frequent. The heavy drinkers suffered more often from pancreatitis, oesophageal varices, polyneuropathy or erectile dysfunction than episodic drinkers. They also showed more upper gastrointestinal disorders, although the estimated life-time alcohol intake was comparable to continuous drinkers. No difference relating to withdrawal delirium or seizures could be found between the groups of alcoholics. Frequent heavy drinkers showed a trend to more alcohol-related medical disorders than alcoholics with a different drinking pattern, although they were younger and their estimated life-time alcohol intake was comparable to that of continuous drinkers. Thus, the drinking pattern, particularly frequent inebriation, has an influence on the occurrence of alcohol-related disorders.     

Treatment of alcoholism and concomitant drugs of abuse

It has been proposed that concomitant substances of abuse may have additive or synergistic properties such that alcoholics using other substances of abuse concurrently may have a harder time giving up alcohol than alcoholics abusing only alcohol. The present study surveyed 291 alcoholics in an alcohol treatment program and 86 social drinker controls matched on age, education, SES and gender. Alcohol consumption, smoking, coffee intake, other substances of abuse. Beck depression and Spielberger Anxiety (State) were measured. Alcoholics drank significantly more alcohol than did social drinkers per day (350.19 cc versus 28.08 cc, p less than 0.001), consumed more caffeine/day (486.3 mg versus 339.9 mg, p less than 0.002), smoked more cigarettes/day (27.8 versus 12.8, p less than 0.001), were more depressed (16.8 versus 4.4 (Beck), p less than 0.0001), had lower internal locus of control scores (37.6 versus 39.7, p less than 0.005), had higher scores on control by chance (22.7 versus 20.2, p less than 0.03) and were significantly more anxious (52.5 versus 33.9 on Spielberger's State Inventory p less than 0.0001). Some patients used stimulants, tranquilizers, depressants, narcotics or toluene. Only 3/258 abused alcohol without using other drugs. Results support earlier studies showing strong associations between alcohol and smoking and between alcohol and caffeine consumption. The alcoholic abusing only alcohol is very rare. Treatment programs need to pay attention to concomitant drugs of abuse.     

Alcohol and Other Drug Use and Automobile Safety: A Survey of Boston-Area Teen-agers

To provide educators with information regarding students' behaviors and beliefs about drinking, drug use and driving, the authors surveyed a stratified random sample of approximately 2,000 seventh and 10th graders in the Boston area in the spring of 1982. The focus of the present paper is on those students who might be most at risk for operating a motor vehicle under the influence of alcohol or marijuana. Therefore, the analysis presented here is limited to 623 students who were 16 years of age or older at the time of the survey.
About half of the students in this age group used alcohol (63%) or marijuana (44%) and as many as 18% had used other illicit drugs during the 1982 school year. While most current drinkers (72%) drank not more than three times a month, nearly half (46%) of the current marijuana users smoked at least once a week.
A substantial proportion of students combined drug and/or alcohol use with driving. Between 43% and 50% had been a passenger with a driver who was under the influence of alcohol or marijuana at least once since the beginning of the school year. Many students did not appear to be aware of the dangers involved in driving under the influence of alcohol or marijuana and about one out of four believed they could use alcohol and other drugs responsibly.
Both students' behaviors and beliefs regarding drinking, drug use and driving were significantly related to the extent of their involvement with alcohol and other drugs. Frequent marijuana users, heavier drinkers and students who used drugs other than alcohol or marijuana were more likely than other students to combine drug use and driving and believe that these activities could be combined safely. The data suggest that the entire constellation of risk-taking and drug-using behaviors should be addressed in educational programs and that information on the effects of other drugs (both alone and in combination with alcohol) on driving ability should be emphasized.     

PSYCHOPHYSIOLOGICAL DIAGNOSTICS IN ALCOHOL DEPENDENCY: FOURIER ANALYSIS OF PUPILLARY OSCILLATIONS AND THE RECEPTOR TEST FOR DETERMINATION OF CHOLINERGIC DEFICIENCY

Mnestic disturbances in alcoholics may be related to cholinergicdeficiency as well as to central nervous system inactivation.After instillation of tropicamide, cholinergic receptors areblocked and pupillary dilatation occurs. It is assumed thatthe more severe the cognitive deterioration, the wider the pupillarydilatation. Pupillary oscillations reflect central activation.Changes of pupillary diameter after topical instillation oftropicamide and pupillary oscillations were measured in 44 alcohol-dependentpatients aged 40–55 years, diagnosed according to theDSM-III-R as severe alcoholics (>7 symptoms), having beenabstinent for at least 3 weeks (objectively tested with carbohydrate-deficienttransferrin), compared with 18 healthy controls. The pupillarydiameter of the left eye was measured eight times within 103min, as were pupillary oscillations. Using Fourier analysis,the amplitudes of oscillations were measured in five frequencybands and the sum of the frequency bands was calculated. Inaddition, central activation was measured during a calculationtest at 3 and 103 min. The pupillary dilatation of 22% in alcoholics compared to 14percnt;of normal controls after tropicamide raises the question ofa cholinergic deficit in alcohol dependence. With regard tobasic activation, measured by Fourier analysis of pupillaryoscillations, alcoholics demonstrated significantly lower power(sum of the frequency bands) than controls at baseline and at3, 20, and 40 min (P < 0.01) as well as at 60, 80, 100, and103 min {P < 0.05). After a cognitive task, a differenceberween alcoholics and healthy controls was found at 3 min.Alcoholics showed lower basic activation and decreased cognitiveactivation. By means of cross-validation, a differentiationbetween alcohol-dependent patients (n = 44 and n = 42 respectively)and normal controls (n = 18) was possible.     

Alcoholic parents and their children

Summary Some 211 male alcoholic in-patients were compared with a simple random sample of 200 men from Greater Stockholm. The group of male alcoholic in-patients and the random sample were subdivided with respect to alcohol consumption and use of hepatotoxic drugs: (IA) men from the random sample with low or moderate alcohol consumption and no use of drugs (n= 169); (IB) men from the random sample with low or moderate alcohol consumption with use of drugs (n= 31); (IIA) alcoholic in-patients with use of alcohol but no drugs (n= 171); (IIB) alcoholic in-patients with use of alcohol and drugs (n= 40). Earlier and more severe alcohol-related and anti-social problems were found among subjects with an alcoholic parent than among subjects without an alcoholic parent. The highest level of problems was noted for subjects with alcoholism in both parents and among the alcoholic in-patients. Groups which resembled each other were the drug users in the alcoholic group and in the general sample. Both inherited and environmental factors are important determinants and many of these individuals have psycho-social problems as children and adults. The children of those adults who used alcohol in combination with drugs (IIB) had most problems and the most severe problems. In the general population sample, those who used alcohol in combination with drugs (IB) had so many problems in the family and psycho-social problems themselves that they resembled the alcoholic in-patients and especially the group with high alcohol consumption in combination with drugs (IIB). A new finding is that the high-risk groups IB and IIB, who used both alcohol and drugs, had experienced a more disturbed school career and were more aggressive, had more nervous problems, and were more emotionally disturbed than the population studied belonged to a concealed alcoholic group raises the question whether it is really true that every sixth inhabitant of Greater Stockholm has a serious alcohol problem. However, the sample was relatively small, and this implies some uncertainty in the determination of the prevalence. A finding that indicates that the figure is not in fact so far from reality is that 65% of group IB were themselves of the opinion that they drank alcohol often or regarded themselves as alcoholics.     

No association between metabotropic glutamate receptors 7 and 8 (mGlur7 and mGlur8) gene polymorphisms and withdrawal seizures and delirium tremens in alcohol-dependent individuals

- Up-regulation of the glutamatergic neurotransmission from chronic ethanol intoxication may cause a hyperexcitable state during alcohol withdrawal that may lead to seizures and delirium tremens. The aim of our study was to evaluate the association between a history of alcohol withdrawal-induced seizures and delirium tremens and a mGlurR7 (Tyr433Phe); and a mGlurR8 (C2756T) metabotropic glutamate receptor polymorphism in alcoholics compared to controls. A total of 182 patients meeting DSM-IV alcohol dependence criteria and 117 controls, both groups being of German descent, were investigated. mGluR7 and mGluR8 polymorphisms were determined using polymerase chain reaction of lymphocyte DNA. History of alcohol withdrawal-induced delirium tremens and seizures were obtained using the Semi-Structured Assessment of Genetics in Alcoholism (SSAGA). Data were cross-checked with inpatients' clinical files. No significant associations were obtained between both receptor polymorphisms and alcohol withdrawal-induced seizures and delirium tremens. The negative results in this study question the role of these polymorphisms in the pathogenesis of alcohol withdrawal-induced seizures and delirium tremens.     

Perceived intensity and pleasantness of sucrose taste in male alcoholics

AIMS: The aim of the present study was to evaluate a possible relationship between taste responses to sweet solutions and alcoholic status. METHODS: The rated intensity and pleasantness of sucrose taste was compared in male alcoholics (n = 45) and non-alcoholic controls (n = 33). RESULTS: The rated intensity, but not pleasantness, of water taste (0% sucrose) was higher in the alcoholics. The two groups did not differ with respect to the rated intensity or pleasantness of sucrose solutions (1-30%). The proportion of sweet-likers, i.e. subjects rating 30% sucrose as most pleasant, was similar in both groups (the controls: 57.6%, the alcoholics: 62.2%). A subgroup of alcoholics with a paternal history of alcoholism (n = 22) rated the highest sucrose concentration as more pleasant compared to alcoholics without alcoholic fathers. The proportion of sweet-likers among the alcoholics with a paternal history of alcoholism (77.3%) was significantly higher than that found in the alcoholics without a familial history of alcoholism (47.8%). CONCLUSIONS: The present results suggest the following: (i) alcohol dependence is not associated with any major alterations in taste responses to sucrose solutions, (ii) sweet liking is a phenotypic marker of male alcoholics with a paternal history of alcoholism.     

Relapse prevention in alcoholics by cigarette smoking? Involvement of nicotinic-dopaminergic mechanisms.

Because of a controversial view on the role of smoking in the recovery process of alcoholism, outcome data obtained for alcoholics who had been included in a long-term clinical trial with a putative anticraving drug were analyzed. To avoid unknown interactions between the drug under study and smoking behavior, only placebo-treated patients were evaluated in this investigation. After 12 months of rehabilitation, there was no significant difference regarding abstinence rate between 48 smoking alcoholics (who reported that they smoked 32 cigarettes on average per day) and 15 nonsmoking alcoholics (33% vs. 20%). However, smokers tended to be abstinent longer than nonsmokers (173 vs. 114 days; P= .092). This possible advantage might be related to nicotinic effects on central dopamine systems in smokers, as indicated by higher growth hormone secretion after apomorphine stimulation obtained in smokers, compared with findings for nonsmokers (area under the curve during chronic intoxication: 2253 vs. 1247 microg/min/l; P= .019). Multivariate regression analysis revealed a decreasing effect of ethanol blood level (P= .006) and the number of fullfilled International Classification of Diseases, 10th edition (ICD-10) criteria of the alcohol dependence syndrome (P= .012) on stimulated growth hormone secretion. In contrast, the reported number of smoked cigarettes per day had an increasing effect (P= .034), accounting for 6% of the variance of growth hormone secretion. However, differences in outcome could also be explained by other clinical features as smokers, compared with nonsmokers, were more frequently males (78.3% vs. 60.7%) and younger when studied at index episode (mean age 44.45 vs. 48.21 years; P= .054), reported higher ethanol consumption in the month before hospital admission (262 g vs. 192 g; P= .044), and met more criteria for the ICD-10 alcohol dependence syndrome (6.6 vs. 6.0; P= .047). Therefore, it cannot be stringently inferred from our data that a possible advantage of smoking for alcoholism recovery is causally related to the effects of nicotine on cerebral systems or human behavior, as our findings had not been based on a randomized design.     

Presence of Alcohol and Drugs in Hispanic Versus Non-Hispanic Youth Suicide Victims in Miami-Dade County,Florida

This study examines the association between the presence of drugs and alcohol at time of suicide in Hispanic versus non-Hispanic youth suicide victims in Miami-Dade County, Florida. The Medical Examiner’s records of 435 persons aged 24 years or younger classified as suicides in Miami-Dade County, Florida, from 1990 to 2011 were reviewed. Hispanic youth in Miami-Dade County, Florida were 1.62 times more likely than non-Hispanic youth to have used drugs and alcohol at time of suicide (OR 1.62; 95 % CI 1.07–2.04; p = 0.049). Firearm use was significantly associated with drug and alcohol use at time of death. Use of drugs and alcohol at the time of death are important risk factors for suicide in Hispanic youth.     

WHEN ALCOHOLICS DRINK AFTERSHAVE: A STUDY OF NONBEVERAGE ALCOHOL CONSUMERS

A one-year prospective study was conducted to describe nonbeveragealcohol (NBA) consumption (the use of substitutes for traditionalforms of ethanol) among alcoholics. It was found that 11% ofinpatient alcoholics at a veterans' hospital and 8.6% of alcoholicsat a community hospital had consumed NBA. Substances consumedranged from toiletries to organic solvents, often in quantitiesexceeding the theoretical lethal dose. ‘Ready availability’was cited as the primary reason for consumption. Social, demographicand psychiatric parameters were then compared between 48 VAalcoholics who used NBA and 48 nonusing alcoholics. No socialor demographic differences were found, but NBA drinkers drankmore alcohol (P < 0.0001), had higher global alcoholic severityscores (P < 0.0001), more severe withdrawal symptoms (P <0.0001), and a higher frequency of antisocial personality disorder(P = 0.009) and drug abuse (P = 0.005). When NBA drinkers weresubdivided by quantity of NBA consumption and recency of latestingestion, no social or psychological differences were foundbetween groups, except for more frequent and heavier illicitdrug use among ‘heavy’ NBA consumers (P < 0.0001).     

5-HT1A Receptors in the Frontal Cortical Brain Areas in Cloninger Type 1 and 2 Alcoholics Measured by Whole-Hemisphere Autoradiography

Aims: The Cloninger type 1 alcoholics are prone to anxiety,and in many cases patients have begun to use alcohol in orderto relieve their anxiety. We have previously reported a decreaseof the serotonin transporter density in the perigenual anteriorcingulate cortex (pACC) in type 1 alcoholics. The 5-HT_1A receptorsare the binding sites for anxiolytic drug buspirone. We aimedto investigate the alteration in the density of 5-HT_1A receptors,that may also alter the effect of serotonin in the pACC in alcoholics.Methods: The density of the serotonin receptor 5-HT_1A amongCloninger type 1 and 2 alcoholics (nine and eight subjects,respectively) and 10 control subjects were determined by postmortemwhole-hemisphere autoradiography with WAY-100635. Results: Substantiallysparser 5-HT_1A (by –31%, P = 0.010) density was observedin the pACC of alcoholic subjects in relation to non-alcoholiccomparison subjects. In a secondary analysis for the differencebetween the alcoholic subtypes and controls, the 5-HT_1A densitywas decreased significantly by –32% (P = 0.015) in theupper level of pACC in type 1 alcoholics. Conclusions: The detecteddecrease of 5-HT_1A receptor density on the pACC suggests furtherthat the serotoninergic system is defected in the so-calledaffect region, especially in the type 1 alcoholics.