Biomedical subjects

J D Higley

Publications and source records attributed to J D Higley.

At least 37 records · Page 2Linked to original sources

PubMed2000

Hormonal correlates of hand preference in free-ranging primates.

In this research we examined hormonal correlates of hand preference in free-ranging primates. Specifically, we tested the hypothesis that levels of the stress hormone cortisol and the male sex hormone testosterone are correlated with handedness in male rhesus macaques (Macaca mulatta). We found significant positive relationships between cortisol and testosterone levels sampled during adolescence and the frequency of right- versus left-hand use sampled during adulthood. These data indicate that adolescent measures of cortisol and testosterone are correlated with hemispheric specialization in adult free-ranging primates.

Adrenocorticotropic Hormone↗

PubMed2000

Seasonal variation in CSF 5-HIAA concentrations in male rhesus macaques.

Seasonal changes in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations were assessed on multiple occasions in 103 free-ranging male rhesus macaques (Macaca mulatta). At the time of sampling subjects ranged between the ages of 2 and 6 years. CSF samples were collected between the hours of 0900 and 1600 throughout the Fall, Winter, and Spring from 1990 through 1994. Data were analyzed in a general linear mixed model with random intercepts. Results indicated that CSF 5-HIAA concentrations decreased with age. CSF 5-HIAA concentrations were significantly increased in the Fall (October and November), which is the height of the breeding season, with no evidence of differences between Winter and Spring. There was also some evidence that the seasonal variation in CSF 5-HIAA concentrations was blunted in younger, more immature subjects.

Aging↗

PubMed2000

CSF 5-HIAA and nighttime activity in free-ranging primates.

Men with low CNS serotonin turnover, as measured by cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) concentrations, exhibit aberrant circadian activity patterns characterized by disrupted sleep rhythms and daytime hyperactivity. To assess whether similar patterns are found in nonhuman primates we examined the relationships between CSF 5-HIAA and nighttime activity in free-ranging monkeys. CSF samples were obtained from 16 adult male rhesus macaques living on a 475 acre, heavily forested sea island. Each subject was captured, fitted with a radio-telemetry motion-detector collar, and then released back into its group. A receiver placed near the sleeping trees of the study subjects recorded activity between 2100 hrs and 0600 hrs. Trained observers recorded behavioral data during the day. The animals followed a typical diurnal activity pattern, as they were active 74% of the sampled time during the day and 37% of the sampled time during the night. CSF 5-HIAA concentrations were inversely correlated with total duration of nighttime activity as well as mean duration of all active events. Nighttime activity was inversely correlated with daytime activity. CSF 3-methoxy-hydroxyphenylglycol (MHPG) concentrations were positively correlated with total nighttime activity, and inversely correlated with daytime sleep frequency. We conclude that male rhesus with low CSF 5-HIAA concentrations have higher total nighttime activity, longer mean periods of nighttime activity, and sleep more during the day than do males with high CSF 5-HIAA concentrations. This suggests that low serotonergic neurotransmission is associated with aberrant diurnal activity, as evidenced by a disruption of nighttime sleep patterns and a compensatory higher rate of inactivity during the day.

Animals↗

PubMed2000

The suitability of [11C]-alpha-methyl-L-tryptophan as a tracer for serotonin synthesis: studies with dual administration of [11C] and [14C] labeled tracer.

The tracer [11C]-alpha-methyl-L-tryptophan (alphaMTP) has been used to measure brain serotonin synthesis rates with positron emission tomography (PET). To address questions about the accuracy of the kinetic model, [14C]alphaMTP was used to directly measure conversion to [14C]-alpha-methyl-serotonin (alphaM5HT) in monkeys that had been previously studied with PET and [11C]alphaMTP. Four male, fasted, isoflurane-anesthetized rhesus monkeys were studied with [11C]alphaMTP and PET. Immediately after the initial 3-hour scan, a second dose of [11C]alphaMTP was coinjected with 1 mCi of [14C]alphaMTP, and additional PET data were collected. Approximately 90 minutes after the second alphaMTP administration, the animals were killed with an overdose of phenobarbital, and brain samples from 21 regions were taken and analyzed by HPLC. Minimal conversion of alphaMTP to alphaM5HT occurred; HPLC analysis of 14C radioactivity showed that greater than 96% of the total counts were in fractions corresponding to the alphaMTP peak. Brain concentrations of serotonin, tryptophan, 5-hydroxyindole-3-acetic acid, and alphaMTP also were determined fluorometrically using external quantification. Patlak plots generated from PET images acquired over 3 hours showed no time period of linear increase, and final slopes were not significantly different from zero, consistent with the finding of minimal conversion to [14C]alphaM5HT. These data indicate that in the 3-hour period after injection, [11C]alphaMTP is acting predominantly as a tracer of tryptophan uptake, not serotonin synthesis.

Animals↗

PubMed2000

Rearing experiences and stress-induced plasma cortisol as early risk factors for excessive alcohol consumption in nonhuman primates.

BACKGROUND: The purpose of this study was to assess the impact of early rearing and stress-induced rise of plasma cortisol collected during infancy as a biological predictors of adult alcohol consumption in nonhuman primates. METHODS: Ninety-seven female and male rhesus macaques (Macaca mulatta) were investigated. They were reared for their first 6 months of life either without mothers or other adults but with constant access to same-aged peers (peer-reared), or as controls with their mothers (mother-reared). When subjects reached 6 months of age, they underwent a series of four sequential weeks of 4-day social separations. Blood was drawn 1 and 2 hr after initiation of the 4-day separation periods, and the plasma was assayed for plasma cortisol concentrations. When the subjects were young adults (approximately 50 months of age), they were tested for voluntary intake of alcohol for 1 hr per day, 4 days a week, during a period of 5 to 7 weeks under normal living conditions. RESULTS: The social separation challenge increased infant plasma cortisol concentrations, with peer-reared subjects exhibiting higher stress-induced cortisol concentrations than mother-reared animals. Subjects that responded to the social separation challenge with high cortisol levels consumed significantly more alcohol per kilogram of body weight as adults than subjects with a low cortisol response to the separation challenge, regardless of rearing condition. In addition, male and peer-reared subjects consumed significantly more alcohol than female and mother-reared subjects, respectively. CONCLUSIONS: These findings suggest that early rearing experiences, such as adult absence, and high plasma cortisol concentrations early in life after a social separation stressor, are useful psychobiological predictors of future high alcohol consumption among nonhuman primates.

Alcohol Drinking↗

PubMed1999

Salivary prolactin as a marker for central serotonin turnover.

Central nervous system (CNS) serotonin deficits have been linked to many pathological behaviors in both human and nonhuman primates. The plasma prolactin response to fenfluramine has been widely used to assess CNS serotonin functioning in humans. Prolactin is also found as an integrated measure in saliva. We hypothesized that salivary prolactin concentrations would correlate positively with cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) in rhesus monkeys. Twenty-seven adult male and female rhesus macaques (Macaca mulatta) were sampled for concurrent saliva, blood, and CSF. Saliva and blood serum were assayed for prolactin concentrations, and CSF was assayed for 5-HIAA, homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). Salivary prolactin concentrations were positively correlated with CSF 5-HIAA concentrations. No other relationships between any of the measures, including that between salivary prolactin and serum prolactin, were found to be statistically significant. These findings suggest the possibility of using salivary prolactin concentrations as an index of CNS serotonin turnover in humans.

Animals↗

PubMed1999

Trait-like immunological and hematological measures in female rhesus across varied environmental conditions.

In this 2-year longitudinal study, 45 2-year-old female rhesus were observed as they were captured and removed from a free-ranging setting (Phase I), single caged for 1 year (Phase II), and housed in small, stable social groups for an additional year (Phase III). During the study, eight blood samples were taken, and hematological, immunological, and hormonal variables were assayed to determine whether 1) any of the measures would exhibit trait-like, inter-individual longitudinal stability, despite fluctuations in population means induced by Phases I, II, and III; 2) plasma concentrations of cortisol, prolactin, and norepinephrine would be lowest in Phase III, and elevated during the periods of acute and chronic stress associated with Phases I and II; and 3) there would be any evidence of immunosuppression associated with Phases I and II. The results suggest that the majority of hematological/immunological variables were trait-like throughout the study in contrast to plasma cortisol, prolactin, and norepinephrine concentrations. Thus, red blood cells, hemoglobin, hematocrit, platelets, mean corpuscular volume and hemoglobin, as well as white blood cells, the absolute number of CD4+ (T-helper/inducer) cells, the absolute number of CD8+ (T-suppressor/cytotoxic) cells, total T cells (CD2+%), total B cells (CD20+%), and the ratio of CD4+/CD8+ cells were trait-like. The hematological measures were changed dramatically by capture and the subsequent single caging, with most not recovering to presumed baselines until after 12-28 weeks. The immune measures were depressed at capture (excepting B cells), and during 7 months of single caging failed to return to normal levels associated with social housing. We thus conclude that single housing can produce significant, long-term features of immunosuppression. Capture produced significant increases in plasma cortisol, prolactin, and norepinephrine concentrations. Long periods of single caging produced significant increases in plasma prolactin concentrations, indicative of stress-induced anxiety, and may also have been associated with down-regulation of plasma norepinephrine and cortisol concentrations.

Animals↗

PubMed1999

Rhesus macaque (Macaca mulatta) group formation and housing: wounding and reproduction in a specific pathogen free (SPF) colony.

In the present report, we examined the effects of group formation strategy and corral design on wounding and reproduction rates in rhesus macaques. Specifically, we examined group formation using a staged strategy, in which small groups of animals were introduced incrementally over a period of weeks, and a rapid formation strategy, in which all animals were introduced in 1 day. We also examined group formation using a divided corral design that facilitated visual and social separation of individuals, and an undivided corral design that did not facilitate visual or social separation. Dependent measures were wounding and reproductive rates over each of the 2 years that followed group formation. Results indicate that incrementally releasing subgroups of animals, and using a corral design that provides for visual and social separation of individuals, are effective strategies for reducing rates of traumatic wounding when forming multimale-multifemale rhesus macaque breeding groups. However, it must be noted that differences in formation strategy and corral design did not lead to higher reproductive rates. We conclude that incrementally releasing animals in hierarchical subgroups, and using a divided vs. undivided housing design, reduced intra-group wounding and associated demands on veterinary and animal management resources following formation of rhesus macaque breeding groups.

Animals↗

PubMed1999

CSF 5-HIAA and aggression in female macaque monkeys: species and interindividual differences.

RATIONALE: While the relationship among CSF 5-HIAA, impulsivity, and aggression is well characterized in males, its investigation in females is limited, and no studies have assessed its generalizability across primates by making simultaneous comparisons between and within closely-related species. OBJECTIVES: We tested three hypotheses. First, that female rhesus macaques would have lower CSF 5-HIAA concentrations and be more aggressive than would female pigtailed macaques. Second, that females of both macaque species would exhibit an inverse relationship between interindividual differences in CSF 5-HIAA concentrations and rates of severe aggression. Third, that subjects with high CSF 5-HIAA concentrations would be higher in social dominance within their respective groups than would subjects with low CSF 5-HIAA concentrations. METHODS: We obtained CSF samples from 61 individually housed female primates of two closely related species: rhesus macaques (Macaca mulatta) and pigtailed macaques (Macaca nemestrina). We later placed subjects in unisex social groups, and correlated interindividual differences in CSF 5-HIAA with aggression, wounding, and acquisition of social dominance rank. RESULTS: Between-species analyses indicated higher CSF 5-HIAA concentrations in pigtailed macaques, and higher rates of high-intensity aggression, escalated aggression, and wounds requiring medical treatment in rhesus macaques. Within-species analyses indicated that interindividual differences in CSF 5-HIAA concentrations were inversely correlated with escalated aggression and positively correlated with social dominance rank. CONCLUSIONS: These findings show that agonistic and social differences between closely-related species are correlated with CNS serotonin activity, as species that show relatively high rates of severe aggression also tend to have low concentrations of CSF 5-HIAA. We conclude that serotonergic functioning plays an important role in controlling impulses that regulate severe aggression and social dominance relationships in both male and female primates, and that between-species differences in agonistic temperament can be predicted by species typical CNS serotonin functioning.

Aggression↗

PubMed1999

Oral self-administration of ethanol, phencyclidine, methadone, pentobarbital and quinine in rhesus monkeys.

RATIONALE: Simultaneous and sequential drug use among clinical populations is the norm, whereas the pattern of self-administration of multiple drugs among non-human primate populations has not been thoroughly explored. OBJECTIVES: To determine the relationship between the preferences and intakes of a large group of rhesus monkeys exposed to various orally available solutions. METHODS: Thirteen male and eleven female young adult rhesus monkeys (Macaca mulatta) were exposed to orally available drug solutions using a concurrent choice (drug and water) procedure, where fluid delivery was made contingent upon single spout contacts (fixed ratio one). RESULTS: Ethanol (0.25-16% w:v) produced biphasic effects on the number of fluid deliveries obtained, with peak ethanol preferences over water demonstrated at the 1-2% w:v concentrations. No preferences for the N-methyl-d-aspartate receptor antagonist phencyclidine or water were demonstrated at lower concentrations (0. 0078125-0.125 mg/ml) and, at higher concentrations (0.25, 0.5 mg/ml), a preference for water was demonstrated. The mu opioid receptor agonist methadone (0.001-0.3 mg/ml) and the prototypic bitter substance quinine (0.001-0.3 mg/ml) failed to produce preferences for drug or water. A large preference for water over the barbiturate pentobarbital (0.01-3 mg/ml) was also demonstrated. After rank-ordering the subjects based on their drug preferences or intakes, modest to no correlations across drugs were demonstrated. CONCLUSIONS: These results reveal that a robust ethanol preference is not predictive of a preference for drugs of abuse from other classes and suggests that fluid intakes were correlated, irrespective of the presence or absence of drug in the solution.

Administration, Oral↗

PubMed1999

Oral ethanol self-administration in rhesus monkeys: behavioral and neurochemical correlates.

BACKGROUND: Previous research has revealed that orally administered ethanol serves as a reinforcer in nonhuman primates. The purposes of the present study were to examine the relationship between ethanol preferences and intakes in two distinct self-administration contexts and to reveal some of the behavioral and neurochemical correlates of oral ethanol self-administration in monkeys. METHODS: Three cohorts of 13 to 29 rhesus monkeys (Macaca mulatta) were socially housed and given daily, 1-hr, one-spout access to an ethanol solution (8.4%, w/v) sweetened with aspartame. Twelve of these monkeys were subsequently selected, individually housed, and given daily, 2-hr, two-spout access to a range of ethanol concentrations (0.25-16%, w/v) concurrently with water. RESULTS: These monkeys (National Institute on Alcohol Abuse and Alcoholism group) showed a marked preference for ethanol (0.5-4%, w/v) over water, and ethanol preferences were 3-fold greater than those of a second group of 12 monkeys (University of Michigan group) purchased from a commercial vendor. Ethanol consumption was consistent across the self-administration paradigms. Monkeys that consumed large quantities of ethanol under the one-spout, social-housing conditions continued to drink large quantities of ethanol under the two-spout, individual-housing conditions (r = 0.86). An association between ethanol preferences and intakes was also demonstrated. Monkeys with the greatest preferences for ethanol over water under the two-spout choice conditions consumed the largest quantities of ethanol (r = 0.82). Finally, cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations were inversely related to ethanol preference but not to ethanol intake. CONCLUSIONS: These results indicate that ethanol consumption is stable across contexts and is positively correlated with the preference for ethanol over water.

Alcohol Drinking↗

PubMed1998

Effect of tryptophan treatment on self-biting and central nervous system serotonin metabolism in rhesus monkeys (Macaca mulatta).

UNLABELLED: Two studies were conducted to examine the effects of oral L-tryptophan (TRP) supplementation as a treatment for self-injurious behavior (SIB) and to investigate behavior and central serotonin turnover of male rhesus monkeys. In Study One, TRP was administered to seven individually housed rhesus monkeys with a recent history of spontaneous SIB. While the monkeys were on TRP treatment (100 mg/kg twice a day), cisternal cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid increased markedly (p = .0013) above baseline (baseline mean = 207.6 pmol/ml +/- 39; TRP mean = 320.3 pmol/ml +/- 83.4), and the duration of self-biting behavior decreased below baseline (p = .03). In Study Two, 14 individually housed rhesus monkeys without a history of SIB were placed on three different doses of TRP in random order (50, 100, and 200 mg/kg twice a day). TRP had no effect on any behavioral or biochemical variables in the normal monkeys. CONCLUSIONS: Supplemental tryptophan in well-tolerated doses reduced self-biting and increases serotonin turnover rate in male monkeys with a recent history of SIB. The same doses of TRP do not affect behavior or serotonin metabolism in male monkeys without a history of SIB.

Animals↗

PubMed1998

Brain serotonin synthesis rates in rhesus monkeys determined by [11C]alpha-methyl-L-tryptophan and positron emission tomography compared to CSF 5-hydroxyindole-3-acetic acid concentrations.

Twelve male, fasted, anesthetized rhesus monkeys were studied with positron emission tomography (PET) and [11C]alpha-methyl-L-tryptophan (alpha MTP) to determine serotonin synthesis rates as described by Diksic et al. (1991). It was expected that the serotonin synthesis rates determined for the whole brain would be correlated with CSF 5-hydroxyindole-3-acetic acid concentrations, a measure of central serotonin turnover, because both measures were obtained at steady state. However, no significant correlation was found. During data analysis, it was noticed that the calculated serotonin synthesis rates were significantly correlated to free plasma tryptophan (TP) concentrations (r = 0.88, p < .001). From repeat scans conducted in six monkeys, it was determined that day-to-day variability in free plasma TP and the percentage of protein binding (average percent difference was 48 and 37%, respectively) produced most of the variability in the calculated serotonin synthesis rates (50%); repeat K images, obtained from the PET data alone, differed by only 11%. Calculated serotonin synthesis rates reported for [11C]alpha MTP PET studies of humans (Nishizawa et al. 1997) and dogs (Diksic et al. 1991) were also highly correlated to reported differences in plasma free TP concentrations. It seems that the [11C]alpha MTP model for the computation of serotonin synthesis rates is very dependent on plasma free TP concentration and that it may not accurately determine actual serotonin synthesis rates.

Animals↗

PubMed1998

In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates.

OBJECTIVE: Studies on brain serotonin metabolism in human and nonhuman primates have indicated that dysfunction of serotonin transmission may play a role in the biological vulnerability to dependence on alcohol. Among young men, low sensitivity to alcohol intoxication predicts subsequent alcohol abuse and dependence. METHOD: The authors used single photon emission computed tomography and the radioligand [(I)123]beta-CIT ([(I)123]methyl 3beta-(4-iodophenyl) tropane-2-carboxylate) to measure the availability of serotonin transporters in 11 male rhesus monkeys, and the monkeys were genotyped for a functional polymorphism of the serotonin transporter gene. The 11 monkeys had experienced parental separation after birth; their behavior and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in CSF had been assessed regularly. RESULTS: In the 5-year-old monkeys, there was a significant negative correlation between beta-CIT binding to serotonin transporters in the brainstem and 5-HIAA concentrations in CSF. Animals with greater beta-CIT binding and low CSF 5-HIAA concentrations displayed greater aggressiveness and were less sensitive to alcohol-induced intoxication. The genetic constitution of the serotonin transporter promoter gene did not significantly contribute to the availability of brainstem serotonin transporters as measured by beta-CIT binding. CONCLUSIONS: In adult nonhuman primates who underwent early developmental stress, variables indicating a low serotonin turnover rate were associated with behavior patterns similar to those predisposing to early-onset alcoholism among humans.

Adult↗

PubMed1997

Low central nervous system serotonergic activity is traitlike and correlates with impulsive behavior. A nonhuman primate model investigating genetic and environmental influences on neurotransmission.

We have used nonhuman primates to examine developmental and behavioral correlates of CNS serotonergic activity, as measured by concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). These studies show that interindividual differences in CNS serotonin turnover rate exhibit traitlike qualities and are stable across time and settings, with interindividual differences in CSF 5-HIAA concentrations showing positive correlations across repeated sampling. Primates with low CNS serotonergic activity exhibit behaviors indicative of impaired impulse control, unrestrained aggression, social isolation, and low social dominance. Maternal and paternal genetic influences play major roles in producing low CNS serotonin functioning, beginning early in life. These genetic influences on serotonin functioning are further influenced by early rearing experiences, particularly parental deprivation.

Animals↗

PubMed1997

Rhesus macaques with high CSF 5-HIAA concentrations exhibit early sleep onset.

The relationship between central nervous system serotonergic activity, as reflected by cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and sleep/wakefulness behavior was investigated in socially housed, juvenile rhesus macaques. Two cohorts of rhesus monkeys (Macaca mulatta), numbering 42 subjects (seventeen 39-month-olds and twenty-five 20-month-olds) were observed in their home cages between 21.30 h and 23.30 h for 10 nights using an infrared night scope. Over each 90-min observation period, the following states were recorded every 5 min using a scan sampling procedure: Sleep, Drowsy, Passive-awake and Active. After more than one quarter of the animals in the group had fallen asleep, states were recorded as they occurred. Six weeks prior to the collection of the behavioral data, a sample of cisternal CSF was obtained to assay for 5-HIAA concentrations. With cohort effects statistically controlled, there was a negative correlation between latency to fall asleep and CSF 5-HIAA concentrations (i.e., subjects with high CSF 5-HIAA concentrations were more likely to fall asleep early). Subjects with low CSF 5-HIAA concentrations were also more active during the daytime hours. Subjects who fell asleep first were, on average, also less active during nighttime hours. The positive correlation between CSF 5-HIAA and sleep onset was not a result of social status since there was no correlation between social dominance rank and time of sleep onset. These results support the hypothesis that the serotonergic system may play a role in sleep onset and possibly in the regulation of diurnal activity rhythms in non-human primates.

Animals↗

PubMed1997

CSF 5-HIAA, testosterone, and sociosexual behaviors in free-ranging male rhesus macaques in the mating season.

This study examines sexual behavior, serotonin turnover in the central nervous system, and testosterone in free-ranging non-human primates. Study subjects were 33 young adult male rhesus macaques (Macaca mulatta) living in naturalistic social groups on a 475-acre South Carolina barrier island. Blood and cerebrospinal fluid (CSF) samples were obtained during random trappings, and the subjects were located for observation by radio telemetry. Quantitative behavioral samples totaling 203 observation hours were taken during two mating seasons (September through January) in 1994 and 1995. Control observations (65 h) on 13 subjects were also taken during the non-mating seasons in 1994 and 1995. The results indicate that CSF 5-hydroxyindoleacetic acid (5-HIAA), CSF testosterone, and plasma testosterone concentrations increase significantly during the mating season. During the mating season, there were significant increases in high intensity aggression, low intensity aggression, grooming behavior, and heterosexual mounting. In the mating season, CSF 5-HIAA was significantly correlated with several sociosexual behaviors: consorts per hour, heterosexual mounts per hour, and inseminations per hour. In contrast to previous findings from the non-mating season, CSF 5-HIAA was not correlated with any measures of aggression or sociality, although during consorting, CSF 5-HIAA was positively correlated with grooming. From these findings, we conclude that the lack of correlation between intense and severe aggression and CSF 5-HIAA in the mating season may reflect the use of high intensity aggression in 'normative' male-male competition over access to reproductively active females. We also conclude that CNS serotonin turnover is positively correlated with sexual competence, i.e. males with low CSF 5-HIAA concentrations are less sexually competent than males with higher concentrations.

Aggression↗

PubMed1997

A nonhuman primate model of excessive alcohol intake. Personality and neurobiological parallels of type I- and type II-like alcoholism.

Developmental, biochemical, and behavioral concomitants of voluntary excessive alcohol consumption were investigated using a nonhuman primate model. Studies were designed to investigate potential neurobiological and behavioral parallels of Cloninger's subtypes of type I and type II alcoholism in nonhuman primates. The studies have shown that a subpopulation of primates chronically consume intoxicating amounts of alcohol. Subjects that chronically consume intoxicating amounts of alcohol often exhibit neurobiological and behavioral features that were predicted by Cloninger's model for subtypes of alcoholism among humans. Investigations showed that behavior patterns and biological indices that characterize high anxiety, whether constitutionally or stress induced, were correlated with high rates of alcohol consumption, consistent with predictions for type I alcoholism. Early untoward rearing experiences that increased anxiety increased the probability that subjects would chronically drink alcohol to intoxication. Investigations of type II-like alcohol consumption patterns focused on subjects with low central nervous system (CNS) serotonin functioning [as measured by reduced cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA)]. CSF 5-HIAA in infancy was shown to be a relatively stable neurobiological trait across development into adulthood. An individual CSF 5-HIAA concentration in infancy was shown to be a consequence of paternal and maternal genetic influences. Early parental neglect reduced CSF 5-HIAA concentrations. Low CSF 5-HIAA and CNS norepinephrine functioning were shown to predict excessive alcohol consumption in adolescence. Behaviorally, subjects with low CSF 5-HIAA demonstrated impaired impulse control, which resulted in excessive and inappropriate aggression, infrequent and inept social behaviors, low social status, social isolation and expulsion from social groups at an early age, and high rates of early mortality. With some exceptions, these findings were consistent with predictions from Cloninger's type II model of excessive alcohol consumption among men who exhibit impaired impulse control and violent and antisocial behaviors.

Alcoholic Intoxication↗