NOT UPDATED - PI LEFT 5/31/06. Increased oral alcohol intake in rhesus macaques after prior exposure to ethanol and parental absence.? Drs. Chen and Schwandt performed a series of studies examining whether early exposure to alcohol would lead to an increased intake of alcohol later in life. Subjects were reared with their mothers in social groups (MR) or without adults in peer-only groups (PR). At a mean age of 3 years, animals were administered a 2.2 gm/kg (males) or 2.0 gm/kg (females) IV dose of alcohol that produced intoxication. Months later, subjects were allowed to drink an 8.4% aspartame-sweetened alcohol solution. Dr. Chen found higher intake in the animals that were pretreated with IV alcohol. Furthermore, alcohol intake was particularly higher in the PR than in the MR subjects. These results revealed that exposure to alcohol early in life may lead to an increased risk for high consumption and that early adult absence may exacerbate this effect. Dr. Schwandt assessed oral alcohol intake in preadolescent juveniles and found that when compared to adolescents, younger juvenile monkeys drink more alcohol. Furthermore, the pattern of consumption over the 6 weeks of testing is different in juvenile subjects: whereas older adolescents show little change or an increase in alcohol consumption across the 6 weeks, juvenile monkeys show a steady decrease in the amount of alcohol consumed across the 6 weeks. These subjects will be tested later to see if early oral intake augments adolescent alcohol binging and intake.? Decreased CNS serotonin turnover, early-life stress, and initial response to ethanol are predictors of ethanol consumption in adolescent rhesus macaques.? Drs. Chen and Schwandt also examined the relationship between CNS serotonin activity, the response to the motor-impairing effects of alcohol, and subsequent alcohol consumption,. One month after cerebrospinal fluid (CSF) was obtained, animals were administered the same IV doses of alcohol described above and rated for degree of intoxication. Animals were later allowed to freely consume a palatable alcohol solution in daily 1-hr sessions until they established a stable intake. Early parental absence, low CSF 5-HIAA, and decreased intoxication to the 2 gm/kg dose of alcohol were predictive of future high alcohol intake. Our findings suggest that low CNS serotonin turnover rate is related to a decreased response to alcohol and is a potential risk factor for increased alcohol consumption. Dr. Schwandt assessed the effects of age on levels of intoxication in adolescent monkeys. She found that when several variables were controlled, younger adolescents were more intoxicated than the older adolescents. There were also several sex differences with younger females showing fewer impaired leaps and less alcohol-induced motor stimulation, while younger males were less likely to show alcohol-induced aggression.? Unlimited access to social ethanol oral self-administration in rhesus macaques: increased drinking during post-stress periods. Chronic alcohol consumption patterns were examined in a social group of adolescent male rhesus macaques given daily 24-hour access to the aspartame-sweetened alcohol solution. Results showed that the monkeys drank more alcohol in the evening, from 4PM to 12AM, than during day-light working hours from 8AM to 4PM. The results also showed that the monkeys drank more during the weekend than the weekdays. The lowest daily intake in alcohol consumption coincided with the Monday-Friday working hours of the research staff, and the hours in which groups of monkeys in adjacent enclosures were captured for scientific study. These findings suggest that during periods of potential stress, rhesus monkeys suppress alcohol intake but as in humans and rodents, monkeys increase their alcohol intake following stressful periods when a threat is no longer present. ? Rearing, Age, Impulse Control and Alcohol Consumption? It is clear that subjects reared without parents consume more alcohol when it is freely available. However, little is known about the mechanisms that produce such high intake. In collaboration with Claudia Fahlke, we investigated the roles of parents (mothers) vs limited social interactions on development, and ultimately as differential contributors to adolescent and adult alcohol intake. Subjects were reared as controls with their parents (MR), without adults but with constant opportunities to interact with same aged peers (PR), or with limited social experience as surrogate-peer-reared (SPR) monkeys. SPR monkeys are provided with a terrycloth-covered surrogate from birth but unlike PR subjects, are limited in their social experiences to a period of one to three hours per day. The PR subjects (which have constant social interactions but no adults present) and SPR subjects exhibit high anxiety and consume more alcohol than MR subjects. On the other hand, when tested over a variety of challenges, MR and PR infants were significantly less inhibited and fearful than SPR infants, and both PR and MR infants were able to adjust better than SPR infants when all groups were challenged with a novel environment and group formation. Furthermore, all of the SPR subjects were low in social dominance rank, a sensitive measure of social competence. Despite these differences in social and emotional behavior, PR and SPR subjects were found to consume alcohol at equal rates.? In a series of performed by Dr. Schwandt and her staff, we hypothesized that SPR monkeys would show evidence of impaired impulse control, as measured by time spent in arms length of an unfamiliar, potentially dangerous intruder, during an Intruder Challenge paradigm. In this paradigm an unfamiliar, same-sexed and same-aged monkey was placed in a small cage adjacent to the home cage. The results showed that the adult SPR animals spent significantly more time within arms length of the intruder when compared to both MR and PR adult monkeys, suggesting impaired impulse control in SPR subjects. These findings suggest that the anxiety-like behaviors and social deficits seen in the SPR subjects are not just a result of parental absence but are also a consequence of early decreased social interactions. Such findings illustrate different influences on normal development but given that the PR and SPR subjects consume alcohol at an equal rate, our findings suggest that parent influence plays an independent role in the risk for excessive alcohol intake.? Several lines of evidence suggest an association of increased alcohol consumption with impulse control deficits in adults. Yet, few studies have focused on the relationship between impulse control deficits and alcohol consumption in preadolescent subjects. In another study, individual differences in the time to approach a stranger at one year of age were used to predict voluntary alcohol consumption at two years of age. Using the same Intruder Challenge Test described above, we quantified the subject?s latency to approach an unfamiliar potentially dangerous intruder. One year later subjects were allowed to freely consume alcohol. Somewhat surprisingly, when compared to previous studies on adults, the preadolescents displayed a delayed latency to approach the intruder, suggesting perhaps high stranger fear in this age group. Consistent with such an interpretation, within that age group an increased latency to approach the stranger directly correlated with alcohol consumption. Our results showed that high anxiety and stranger fear predict high alcohol consumption in preadolescent macaques.
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