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The transcription factor nuclear factor-kappa B (NF-kappaB) is an inducible regulator of genes that plays a crucial role in the nervous system. Glutamate receptor stimulation is one well-described mechanism for NF-kappaB activation. In the studies presented here we used the glutamate analog, kainate to investigate the signaling mechanisms that couple to NF-kappaB activation in hippocampus. Kainate (250 nM) application to hippocampal slices elicited a time-dependent increase in nuclear NF-kappaB levels in areas CA3 and CA1, but not dentate, compared with controls. Further analysis focused on hippocampal area CA3, revealed increased NF-kappaB DNA binding activity in response to kainate stimulation. Supershift electrophoretic mobility shift assay indicated that the kainate-mediated NF-kappaB complex binding DNA was composed of p65, p50, and c-Rel subunits. Through inhibition studies we found that extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol-3 kinase (PI3K) couple to basal and kainate-mediated NF-kappaB DNA binding activity in area CA3. Kainate elicited decreased total and increased phospho-inhibitor kappa B alpha (IkappaBalpha), suggesting that kainate-mediated activation of NF-kappaB is via the classical IkappaB kinase pathway. Interestingly, inhibition of ERK but not PI3K blocked the kainate-mediated increase in phospho-IkappaBalpha. Thus, our findings support a role for the ERK and PI3K pathways in kainate-mediated NF-kappaB activation in hippocampal area CA3, but these kinases may target the NF-kappaB pathway at different loci.

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This report uses data from a nationally representative longitudinal sample to examine the relationship of marijuana use by high school seniors to occupational attainment 10 years later. Analyses were conducted separately by gender, with and without controlling for other variables. Control variables, all measured when respondents were seniors, were: academic performance, educational aspirations, and occupational aspirations. Results indicate that the influence of marijuana use on occupational attainment is considerably different for males and females.

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Researchers have seldom examined whether risk and protective factors are consistently linked to substance use across historical time. Using nationally representative data collected from 22 consecutive cohorts of high school seniors (approximate N = 188,000) from the Monitoring the Future (MTF) project, we investigated whether correlates of substance use changed across historical time. We found a high degree of consistency across historical time in predictors of past month cigarette use, past month alcohol use, past year marijuana use, and past year cocaine use. Some predictors such as religiosity, political beliefs, truancy, and frequent evenings out were consistently linked to substance use. The consistency of other predictors such as region, parental education, and college plans was contingent in part upon historical time period, the particular substance, and its level of use.

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Conditioned stimuli (CS) can be devalued by exposure to those stimuli in the absence of primary reward. We tested the hypothesis that dopamine (DA) mediates the control of behavior by conditioned appetitive stimuli. Long-Evans rats were trained to respond for sucrose under a heterogeneous chain schedule in which seeking responses (lever press) turned on a houselight [variable interval (VI)-120 s]; taking responses (wheel turn or chain pull) in the presence of the houselight were reinforced [fixed ratio (FR)-1] by a sucrose pellet. When responding on this schedule was stable, the levers were retracted and subjects had access to the sucrose-taking manipulandum only. Sucrose-taking responses were either extinguished or reinforced under the influence of the DA antagonist, pimozide. Control groups were also reinforced for sucrose-taking responses but received no injection or a vehicle injection prior to each session. Responses of extinction and pimozide-treated groups declined over sessions. Sucrose-seeking responses were measured in a later test when subjects had no access to the sucrose-taking manipulandum or to the reinforcer. Both extinction and pimozide manipulations reduced seeking responses, relative to the respective control groups. Pimozide injections in the home cage had no effect. These data support the idea that DA mediates the conditioned reinforcing properties provided by access to the taking link of the chain.

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The distribution of inositol 1,4,5-trisphosphate (IP(3)) receptor type 1 (IP(3)R1) protein was studied in the adult cerebella of six different vertebrate species, zebrafish, skate, claw frog, rat, hamster, and mouse. The receptor was found at high expression levels in Purkinje cells in all species examined using a subtype-specific polyclonal antiserum against IP(3)R1 and fluorescence immunocytochemistry. The immunoreactivity for IP(3)R1 was found intracellularly at high concentrations in dendrites and somata and at lower levels in axons of these cells. Despite the morphological and functional differences of the cerebella the staining patterns of IP(3)R1 labeling in Purkinje cells was preserved. This is notable because the cerebella were taken from organisms representing a large segment of vertebrate phylogenetic development. The high expression levels of IP(3)R1 in Purkinje cells were found independent of the degree of the formation of fissures and folia and of the degree of branching of Purkinje cell dendrites. The conservation of cerebellar structures not only at the cellular level but more importantly at the molecular level suggests that identical intracellular calcium signaling mechanisms are used in a number of species that represent different areas of phylogenetic development and specialization.

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Relations among academic achievement, school bonding, school misbehavior, and cigarette use from 8th to 12th grade were examined in two national panel samples of youth (n = 3056). A series of competing conceptual models developed a priori was tested using structural equation modeling (SEM). The findings suggest that during middle adolescence the predominant direction of influence is from school experiences to cigarette use. School misbehavior and low academic achievement contribute to increased cigarette use over time both directly and indirectly. Two-group SEM analyses involving two cohorts-gender and ethnicity- revealed that our findings are robust. In addition, comparisons between high school dropouts and nondropouts and between eighth-grade cigarette use initiators and nonusers revealed few differences in direction or magnitude of effects. Results suggest that prevention programs that attempt to reduce school misbehavior and academic failure, as well as to help students who misbehave and have difficulty in school constructively avoid negative school- and health-related outcomes, are likely to be effective in reducing adolescent cigarette use.

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OBJECTIVE: Although there is a growing literature on racial/ethnic differences in alcohol, tobacco and other drug use among adolescents, relatively little is known about the social epidemiology of drug use within the black youth population. The purpose of this article is to address this knowledge gap. METHOD: Data from the Monitoring the Future Project are used to examine empirically the prevalence, trends and sociodemographic correlates of drug use among nationally representative samples of black eighth, tenth and twelfth graders (approximate N = 25,000). RESULTS: Alcohol is the drug most widely used by black youth, followed by tobacco and marijuana. By twelfth grade, seven in 10 black secondary students have used alcohol, less than 50% have smoked cigarettes, 25% have used marijuana and less than 2% have used cocaine. Trend data indicate that, although alcohol use has been relatively stable over time, cigarette and marijuana use are increasing. Gender and family structure are significant sociodemographic correlates of drug use, with use being, on average, higher among males than females, and higher among students who do not live with either of their parents than among those who live with at least one of their parents. The relationships between drug use and socioeconomic status, urbanicity and region vary depending on students' grade level and the specific drug in question. CONCLUSIONS: These findings provide an important empirical baseline for future research on the epidemiology and etiology of drug use among young black people.

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OBJECTIVES: The US armed forces adopted "zero tolerance" policies concerning illicit drug use in 1980 and later developed policies to discourage tobacco and alcohol abuse. This article examines drug use among young active-duty recruits both before and after enlistment, compared with nonmilitary age-mates, and documents historical shifts in such drug use across 2 decades. METHODS: Analyses employed longitudinal panel data from 20 nationally representative samples of high school seniors (cohorts of 1976-1995), each surveyed just before graduation and again within 2 years. Separate analyses for men (n = 12,082) and women (n = 15,345) contrasted those who entered military service, college, and civilian employment. RESULTS: Illicit drug use declined more among young military recruits than among their civilian counterparts. Analyses of male recruits at multiple time periods showed (1) declines in the prevalence of marijuana use and cocaine use after the initiation of routine military drug testing and (2) lower proportions of smokers of half a pack or more of cigarettes per day who entered service after the initiation of tobacco bans during basic training. CONCLUSIONS: Recent military drug policies appear to deter illicit drug use among enlistees and discourage some smokers from enlisting.

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OBJECTIVES: This article reports the prevalence of, and trends in, driving after drinking and riding in a car with a driver who has been drinking among American high school seniors, based on data from more than a decade (1984-1997) of annual national surveys. METHODS: Logistic regressions were used to assess the effects of demographic factors (gender, region of country, population density, parental education, and race/ethnicity) and selected "lifestyle" factors (religious commitment, high school grades, truancy, illicit drug use, evenings out per week, and miles driven per week). RESULTS: Rates of adolescent driving after drinking and riding with a driver who had been drinking declined significantly from the mid-1980s to the early or mid-1990s, but the declines have not continued in recent years. Rates of driving or riding after drinking were higher among high school seniors who are male. White, living in the western and northeastern regions of the United States, and living in rural areas. Truancy, number of evenings out, and illicit drug use all related significantly positively with the dependent variables, whereas grade point average and religious commitment had a negative relationship. Miles driven per week related positively to driving after drinking.

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OBJECTIVES: This study identified high school seniors at low, moderate and high risk for cigarette use to examine changes in the prevalence of daily smoking within risk groups from 1976 to 1995. METHODS: Data were taken from the Monitoring the Future Projects national surveys of high school seniors. Risk classification was based on grade point average, truancy, nights out per week, and religious commitment. Logistic regression models were used to estimate trends for all seniors and separately for White (n = 244,221), African American (n = 41,005), and Hispanic (n = 18,457) made and female subgroups. RESULTS: Risk group distribution (low = 45%, moderate = 30%, high = 25%) changed little over time. Between 1976 and 1990, greater absolute declines in smoking occurred among high-risk students (17 percentage points) than among low-risk students (6 percentage points). Particularly large declines occurred among high-risk African Americans and Hispanics. Smoking increased in all risk groups in the 1990s. CONCLUSIONS: Among high school seniors, a large part of the overall change in smoking occurred among high-risk youth. Policies and programs to reduce smoking among youth must have broad appeal, especially to those at the higher end of the risk spectrum.

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Several ongoing national surveys, including the Monitoring the Future study, the National Household Survey on Drug Abuse, and the Youth Risk Behavior Survey, are investigating the drinking behaviors of adolescents in the United States. These studies have found that the majority of adolescents under the age of 18 have consumed alcohol, although the minimum legal drinking age is 21. Drinking rates may even have increased in recent years in some age groups. No substantial differences exist among various sociodemographic subgroups with respect to drinking rates, although alcohol consumption generally is lowest among African-Americans and highest among whites. Moreover, alcohol consumption increases sharply throughout adolescence. Various attitudinal and behavioral factors, such as religious involvement, truancy, and average grade level, also influence adolescents' drinking behaviors. Almost two-thirds of 12th graders who report consuming alcohol experience at least one alcohol-related problem. Most adolescents drink to experience the pleasurable effects of alcohol, such as having a good time with friends.

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This study examines which personal student background and college characteristics are associated with marijuana use. A self-administered survey was mailed to a national representative sample of 17592 students at 140 American colleges. One of four (24.8%) students reported using marijuana within the past year. Rates of use among the colleges ranged from zero per cent at the lowest use schools to 54% at the highest use schools. Multiple regression models, constructed to determine the college and student characteristics predicting marijuana use, suggest that use was higher among students at non-commuter colleges and at colleges with pubs on campus. Student characteristics associated with marijuana use included being single, white, spending more time at parties and socializing with friends, and less time studying. Marijuana use was higher among students who participate in other high risk behaviors such as binge drinking, cigarette smoking and having multiple sexual partners, and among students who perceived parties as important, and religion and community service as not important. The study points to the social nature of drug use in college, and demonstrates that this behavior is of continuing concern for public health.

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One approach to determining the validity of self-reported drug use measures is to examine the extent of logically inconsistent responses over time. Because lifetime use logically should never decline, the rate of subsequent recanting of earlier reported lifetime use provides relevant evidence on validity. In this chapter, recanting rates are examined in nationally representative samples of high school seniors (18-year-olds) surveyed in the Monitoring the Future study as they are followed up on seven occasions through age 32. For the illegal drugs examined (marijuana, cocaine, and lysergic acid diethylamide (LSD)), recanting rates prove to be quite modest, but for the psychotherapeutic drugs, they were more substantial, possibly because of their greater definitional ambiguity. In general, there were no large individual differences in recanting rates as a function of sex, household composition, community size, or education level. Consistent with previous work, minorities (particularly African Americans) had somewhat higher rates of recanting on the illegal drugs. So did respondents in certain occupations, namely, the military and police/firefighting. In general, however, the evidence is quite good for validity of self-reported (by mail) lifetime use of the illegal drugs in young adulthood.

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OBJECTIVE: The purpose of this study was: (1) to identify different trajectories of frequent binge drinking during the transition to young adulthood; (2) to validate the trajectories by relating them to behaviors and attitudes concerning alcohol and other drug use; and (3) to distinguish among the trajectories according to demographic characteristics and lifestyle experiences typical of the transition to young adulthood. METHOD: Four waves of national panel data were obtained from the Monitoring the Future project; 9,945 weighted cases from the 1976-85 high school senior year cohorts were surveyed at biennial intervals between ages 18 and 24. Frequent binge drinking was defined as having five or more drinks in a row at least twice in the past two weeks. RESULTS: Six distinct frequent binge drinking trajectory groups were specified a priori and confirmed with cluster analysis: Never, Rare, Chronic, Decreased, Increased and "Fling." Repeated measures ANOVAS revealed that the trajectories corresponded to patterns of change and stability in problems with alcohol, attitudes about heavy drinking, peer heavy drinking and illicit drug use. Results from logistic regression analyses predicting diverging and converging trajectories provided some support for the general hypothesis that trajectories of Chronic and Increased frequent binge drinking over time are associated with difficulties in negotiating the transition to young adulthood. CONCLUSIONS: The findings provide strong evidence for wide developmental variation in drinking patterns in the population, variation that is obscured by more aggregate-level considerations. The developmental variation in frequent binge drinking during the transition to young adulthood reflects systematic variation in success and difficulties with negotiating the transition.

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This article discusses the epidemiology of adolescent substance use, including licit drugs and illicit drugs. The focus is on nationally representative samples of eighth-, tenth-, and twelfth-grade students from both public and private schools. Prevalence rates and recent trends are discussed for subgroups based on gender, geographic region, population density, parental education, and racial or ethnic groups. Some implications for public policy are presented.

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In this investigation, two indicators of high school educational success (grade point average and college plans) were examined to determine their influence on cigarette, alcohol, and illicit drug use during the transition to young adulthood. Panel data were obtained from the 1978-81 Monitoring the Future nationally representative samples of high school seniors. The sample for this analysis included 3,399 White respondents (weighted cases) followed three to four years post-high school. Structural equation models that included background and mediating characteristics were developed and tested using LISREL VII. Consistent with a selection hypothesis, high school GPA had a negative indirect effect on post-high school substance use that operated largely via senior-year substance use. College plans during high school had a similar negative effect on post-high school cigarette use, but consistent with a differential-socialization hypothesis, they had a positive indirect effect on post-high school alcohol use that operated primarily via student and marital status during young adulthood. College plans had no impact on post-high school illicit drug use.

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BACKGROUND: This paper reports racial/ethnic differences in the use of licit and illicit drugs by high school seniors in the United States. METHODS: The study uses questionnaire data from annual, nationally representative surveys of seniors from 1976 through 1989. Combined sample sizes were 57,620 for 1976-79; 75,772 for 1980-84; and 73,527 for 1985-89. RESULTS: Native American had the highest prevalence rates for cigarettes, alcohol, and most illicit drugs; White students had the next highest rates for most drugs. Asian Americans had the lowest prevalence rates, and Black students had levels nearly as low except for marijuana. Prevalence rates for the Hispanic groups were mostly in the intermediate ranges except for relatively high cocaine use among the males. Trend patterns for most forms of drug use were similar across subgroups, although cigarette use declined more sharply for Black than White seniors, resulting in greater Black-White differences in recent years. CONCLUSIONS: This study, other school-based studies, and general population surveys all show relatively low levels of drug use by most non-White youth, especially Black Americans and Asian Americans. Multivariate analyses indicate that such subgroup differences in high school seniors' drug use are not primarily attributable to family composition, parents' education, region, or urban-rural distinctions.

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Based on the data presented in this chapter, there is clearly no cause for complacency about the problem of cocaine use among the Nation's youth. Lifetime prevalence is at a disturbingly high 15 percent among high school seniors and over 20 percent among college students. Prevalence is considerably higher, around 30 percent, among young adults in the age range of 19 to 28, and reaches nearly 40 percent for people in their late twenties. The use of cocaine is higher among males than among females; higher in the West and Northeast and lower in the North Central and South; and distinctly lower in rural, compared to more urban, areas. The prevalence figures made clear that cocaine use has by no means become a rare behavior among young people. And the new form, crack, has made substantial inroads among these populations. Among high school seniors, more than 1 in 20 have tried crack cocaine. Although these figures are very high, there is encouraging news in the slight downturn in prevalence that occurred in 1986 and particularly in the sharp decline in 1987. Clearly, these declines were not due to any reduction in perceived availability of cocaine, which actually increased. The declines appear to be due primarily to the increasing recognition that cocaine use is dangerous and caries substantial risk of harm. On the other hand, there is reason to be concerned about the situation with respect to crack cocaine. Some indicators suggest that use of crack cocaine is not declining to the same extent that other cocaine use is. Moreover, this study does not represent well the populations of inner cities, with their extraordinarily high dropout rates; it may well be that the epidemic is continuing to grow there.

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This paper explores alternative explanations for the recent sharp decline in cocaine use among high school seniors, using questionnaire data from annual nationwide surveys conducted from 1976 through 1988. Results show important parallels with earlier analyses of the longer-term decline in marijuana use. Although lifestyle factors (e.g., religious commitment, truancy, evenings out for fun and recreation) show strong links with use of marijuana and cocaine, these factors have not developed trends in ways that can account for the declines in use of either drug. Reported availability of either drug has not been reduced. Instead, increases in perceived risks and disapproval appear to have contributed substantially to the recent declines in use of marijuana and cocaine. The findings provide strong support for the use of realistic information about risks and consequences as an important ingredient in efforts to prevent drug use. Coupled with the findings on availability, the results emphasize the importance of efforts to reduce demand (as opposed to supply).

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