Age-dependent effects of low-dose nicotine treatment on cocaine-induced behavioral plasticity in rats

Epidemiological evidence of early adolescent tobacco use, prior to that of marijuana and other illicit drugs, has led to the hypothesis that nicotine is a “gateway” drug that sensitizes reward pathways to the addictive effects of other psychostimulants. To test this hypothesis, we have compared the effect of a brief, low-dose nicotine pretreatment of adolescent and adult rats on subsequent locomotor response to acute and chronic cocaine. Adolescents, aged postnatal day (P) 28, and adults, aged P86, were given four daily injections of saline or nicotine (0.06 mg/kg, i.v.). At P32 and P90, rats were given acute injections of cocaine (0, 0.4 or 1.0 mg/kg, i.v.) and monitored for locomotor activity in either a habituated or novel test environment. To examine cocaine sensitization, rats were treated for 3 days with saline or cocaine (0.4 mg/kg, i.v.), and, after 1 day of withdrawal, were given a challenge dose of cocaine (0.4 mg/kg, i.v.). Nicotine pretreatment did not affect acute, drug-induced locomotor activity at either age. However, age differences in cocaine response were observed, with adolescent animals showing enhanced locomotor activity in the novel environment. Adolescent controls did not exhibit cocaine-induced locomotor sensitization, whereas adults did. Nicotine pretreatment during adolescence promoted the development and expression of a sensitized response to repeated cocaine exposure similar to that observed in saline-pretreated adult controls. These findings show that brief pretreatment with nicotine, in a low dose comparable to that inhaled in 2–4 cigarettes, enhances cocaine-induced behavioral plasticity in adolescent rats

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Adolescents' reactions to participating in ethically sensitive research: A prospective self-report study

Background: Conducting psychological research with adolescents is imperative for better understanding, prevention and treatment of mental illness. However there is concern that research addressing topics such as mental illness, substance use and suicidality has potential to distress participants, particularly youth. Method: We administered a questionnaire to 1973 adolescents (13-18 years) at two time points, one year apart. Participants responded to items regarding nonsuicidal self-injury, psychological distress, history of physical and/or sexual abuse, adverse life events, alcohol use, suicidal behaviour, self-efficacy, and coping skills as well as two open-ended questions regarding whether they enjoyed participating in the research and whether participation worried or upset them. Results: Most youth (74 %) enjoyed participation and cited altruistic reasons and a greater self-awareness as reasons. Those reporting being upset by the questionnaire (15 %) reported poorer psychological functioning than their peers. Youth who were upset by their participation at baseline, but who reported enjoying the questionnaire at follow-up reported improved psychosocial functioning over time, while the reverse was true for those who initially enjoyed participation but later reported the questionnaire upset them. Conclusions: Results suggest researchers acknowledge benefits for young people who participate in research, but also be mindful of the potential for distress among the most at risk youth

Caveats of chronic exogenous corticosterone treatments in adolescent rats and effects on anxiety-like and depressive behavior and hypothalamic-pituitary-adrenal (HPA) axis function

<p>Abstract</p> <p>Background</p> <p>Administration of exogenous corticosterone is an effective preclinical model of depression, but its use has involved primarily adult rodents. Using two different procedures of administration drawn from the literature, we explored the possibility of exogenous corticosterone models in adolescence, a time of heightened risk for mood disorders in humans.</p> <p>Methods</p> <p>In experiment 1, rats were injected with 40 mg/kg corticosterone or vehicle from postnatal days 30 to 45 and compared with no injection controls on behavior in the elevated plus maze (EPM) and the forced swim test (FST). Experiment 2 consisted of three treatments administered to rats from postnatal days 30 to 45 or as adults (days 70 to 85): either corticosterone (400 μg/ml) administered in the drinking water along with 2.5% ethanol, 2.5% ethanol or water only. In addition to testing on EPM, blood samples after the FST were obtained to measure plasma corticosterone. Analysis of variance (ANOVA) and alpha level of <it>P </it>< 0.05 were used to determine statistical significance.</p> <p>Results</p> <p>In experiment 1, corticosterone treatment of adolescent rats increased anxiety in the EPM and decreased immobility in the FST compared to no injection control rats. However, vehicle injected rats were similar to corticosterone injected rats, suggesting that adolescent rats may be highly vulnerable to stress of injection. In experiment 2, the intake of treated water, and thus doses delivered, differed for adolescents and adults, but there were no effects of treatment on behavior in the EPM or FST. Rats that had ingested corticosterone had reduced corticosterone release after the FST. Ethanol vehicle also affected corticosterone release compared to those ingesting water only, but differently for adolescents than for adults.</p> <p>Conclusions</p> <p>The results indicate that several challenges must be overcome before the exogenous corticosterone model can be used effectively in adolescents.</p

From wing to wing: the persistence of long ecological interaction chains in less-disturbed ecosystems

Human impact on biodiversity usually is measured by reduction in species abundance or richness. Just as important, but much more difficult to discern, is the anthropogenic elimination of ecological interactions. Here we report on the persistence of a long ecological interaction chain linking diverse food webs and habitats in the near-pristine portions of a remote Pacific atoll. Using biogeochemical assays, animal tracking, and field surveys we show that seabirds roosting on native trees fertilize soils, increasing coastal nutrients and the abundance of plankton, thus attracting manta rays to native forest coastlines. Partnered observations conducted in regions of this atoll where native trees have been replaced by human propagated palms reveal that this complex interaction chain linking trees to mantas readily breaks down. Taken together these findings provide a compelling example of how anthropogenic disturbance may be contributing to widespread reductions in ecological interaction chain length, thereby isolating and simplifying ecosystems

Exploring types of focused factories in hospital care: a multiple case study

Background: Focusing on specific treatments or diseases is proposed as a way to increase the efficiency of hospital care. The definition of "focus" or "focused factory", however, lacks clarity. Examples in health care literature relate to very different organizations.\ud Our aim was to explore the application of the focused factory concept in hospital care, including an indication of its performance, resulting in a conceptual framework that can be helpful in further identifying different types of focused factories. Thus contributing to the understanding of the diversity of examples found in the literature. - \ud \ud Methods: We conducted a cross-case comparison of four multiple-case studies into hospital care. To cover a broad array of focus, different specialty fields were selected. Each study investigated the organizational context, the degree of focus, and the operational performance. Focus was measured using an instrument translated from industry. Data were collected using both qualitative and quantitative methods and included site visits. A descriptive analysis was performed at the case study and cross-case studies level. - \ud \ud Results: The operational performance per specialty field varied considerably, even when cases showed comparable degrees of focus. Cross-case comparison showed three focus domains. The product domain considered specialty based focused factories that treated patients for a single-specialty, but did not pursue a specific strategy nor adapted work-designs or layouts. The process domain considered delivery based focused factories that treated multiple groups of patients and often pursued strategies to improve efficiency and timeliness and adapted work-designs and physical layouts to minimize delays. The product-process domain considered procedure based focused factories that treated a single well-defined group of patients offering one type of treatment. The strategic focusing decisions and the design of the care delivery system appeared especially important for delivery and procedure based focused factories. - \ud \ud Conclusions: Focus in hospital care relates to limitations on the patient group treated and the range of services offered. Based on these two dimensions, we identified three types of focused factories: specialty based, delivery based, and procedure based. Focus could lead to better operational performance, but only when clear strategic focusing decisions are made

Effects of Attractiveness and Social Status on Dating Desire in Heterosexual Adolescents: An Experimental Study

The present study examined to what extent adolescent dating desire is based on attractiveness and social status of a potential short-term partner. Further, we tested whether self-perceived mate value moderated the relationship between dating desire and attractiveness of a potential partner. Data were used from a sample of 1,913 adolescents aged 13–18. Participants rated the importance of various characteristics of a potential partner and also participated in an experimental vignette study in which dating desire was measured with either low or high attractive potential partners having either a high or low social status. The results showed that boys rated attractiveness as more important than girls, while social status was rated as relatively unimportant by both sexes. In addition, in the experimental vignette study, it was found that attractiveness was the primary factor for boys’ dating desire. Only when a potential partner was attractive, social status became important for boys’ dating desire. For girls, on the other hand, it appeared that both attractiveness and social status of a potential partner were important for their dating desire. Finally, boys and girls who perceived themselves as having a high mate value showed more dating desire toward an attractive potential partner compared to adolescents who perceived themselves as having a low mate value. The present results extend previous research by showing that attractiveness of a potential partner is important to both adolescent boys and girls, but social status does not strongly affect dating desire during this particular age period

Altered Risk-Based Decision Making following Adolescent Alcohol Use Results from an Imbalance in Reinforcement Learning in Rats

Alcohol use during adolescence has profound and enduring consequences on decision-making under risk. However, the fundamental psychological processes underlying these changes are unknown. Here, we show that alcohol use produces over-fast learning for better-than-expected, but not worse-than-expected, outcomes without altering subjective reward valuation. We constructed a simple reinforcement learning model to simulate altered decision making using behavioral parameters extracted from rats with a history of adolescent alcohol use. Remarkably, the learning imbalance alone was sufficient to simulate the divergence in choice behavior observed between these groups of animals. These findings identify a selective alteration in reinforcement learning following adolescent alcohol use that can account for a robust change in risk-based decision making persisting into later life