The Nature of 3, 4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonergic Dysfunction: Evidence for and Against the Neurodegeneration Hypothesis

High doses of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) have been well-documented to reduce the expression of serotonergic markers in several forebrain regions of rats and nonhuman primates. Neuroimaging studies further suggest that at least one of these markers, the plasma membrane serotonin transporter (SERT), may also be reduced in heavy Ecstasy users. Such effects, particularly when observed in experimental animal models, have generally been interpreted as reflecting a loss of serotonergic fibers and terminals following MDMA exposure. This view has been challenged, however, based on the finding that MDMA usually does not elicit glial cell reactions known to occur in response to central nervous system (CNS) damage. The aim of this review is to address both sides of the MDMA-neurotoxicity controversy, including recent findings from our laboratory regarding the potential of MDMA to induce serotonergic damage in a rat binge model. Our data add to the growing literature implicating neuroregulatory mechanisms underlying MDMA-induced serotonergic dysfunction and questioning the need to invoke a degenerative response to explain such dysfunction

Stressing the Hormone: Biological and Psychosocial Factors associated with Chronic Stress

Chronic stress has been associated with a constellation of deleterious psychological and physical health outcomes. We collected cortisol from hair (CORT) to assess chronic stress retrospectively for 3 months’ time (3cms). Over two studies from the UMass Boston campus and the local community, we recruited in t1: 134 adults (ages 18-67; M = 29.49, SD = 12.48) and t2: 145 adults (ages18-30, M = 22.56, SD = 3.54) to participate on two studies assessing objective biological stress (via hair cortisol), subjective perceived stress (via self-reports), psychosocial factors, and health indicators. In follow-up Study 2, we also included indices of perceived discrimination, cardiovascular parameters, and affective vigilance. Results: t1: CORT levels were positively associated with Total perceived stress and one health indicator: systolic blood pressure. An SES by Race interaction predicted both higher CORT and perceived stress, although higher SES did not always confer the expected benefit of higher SES: minorities in high SES had the greatest CORT, systolic blood pressure, and lowest self-rated health. Results: t2: Perceived stress measures and new measures of discrimination were negatively associated with well-being and health. Higher racial/ethnic pride was associated with better health, but also increased daily discrimination and waist-to-hip ratio. The SES by Race interaction was again associated with Total perceived stress and minorities in higher SES reported greatest Total stress. Minorities also showed the greatest vigilance. Specifically, African-Americans had the longest latencies for social devaluation words during a modified Stroop, the greatest city stress, and the greatest pride/identity for heritage group

Objective and Subjective Stress Differences: Foreign-Born and U.S. Native Adults in Boston Communities

This study compares two high-risk populations: foreign- and US-born adults residing in the same Boston neighborhoods noted for high violence, low income, and greater morbidity and mortality for several chronic diseases (Health of Boston, 2010). The aims of the study are to improve community engagement and to identify stress-related differences between foreign and US-born adults and the interrelations between physiological and subjective stress indices in these populations. This presentation is part of the mini-symposium titled: How Community-Academic Partnership Initiatives Can Contribute to Translational Research

Relationships between affiliative social behavior and hair cortisol concentrations in semi-free ranging rhesus monkeys

Sociality is a fundamental aspect of human behavior and health. One benefit of affiliative social relationships is reduced short-term levels of glucocorticoids (GCs), which are indicative of physiological stress. Less is known, however, about chronic GC production in relation to affiliative social behavior. To address this issue, we studied a semi-free ranging troop of rhesus macaques (Macaca mulatta) and collected hair samples to measure hair cortisol concentrations (HCCs), as a measure of chronic GC production, during routine biannual exams. We collected social behavior (both aggressive and affiliative) and hair samples for 32 adult female rhesus macaques over one year (Experiment 1). Our results indicated that adult females who initiated higher levels of social affiliation had significantly lower levels of HCCs. Neither the initiation nor the receipt of aggression were significantly related to HCCs in this study. In a second experiment we studied 28 mother-infant dyads for the first 90 days postpartum to examine mother-infant facial interactions (i.e. mutual gazing). We analyzed HCCs during weaning approximately one year later, which is a major transitional period. We found that infants that engaged in higher levels of mutual gazing in the first 90 days postpartum had significantly lower levels of HCCs during weaning. Finally, we studied 17 infant rhesus macaques (13 males) to examine whether social behavior (such as play) in the first five months of life correlated with infant HCCs over those months (Experiment 3). We found that infant males that engaged in more social play had significantly lower levels of HCCs. By relying on an animal model, our study shows that affiliative social traits are associated with lower long-term GC production. Future research should address the complex interactions between social behavior, chronic GC production, and mental and physical health

Genetic evidence of Dobrava virus in Apodemus agrarius in Hungary.

Using nested polymerase chain reaction, we sequenced Dobrava virus (DOB) from the rodent Apodemus agrarius in Hungary. The samples we isolated group with DOB samples previously isolated from A. flavicollis. This grouping may indicate host switching

Matrilineal behavioral and physiological changes following the death of a non-alpha matriarch in rhesus macaque

In many species, the loss of alpha matriarchs is associated with a number of negative outcomes such as troop fission, eviction, wounding, and reduced vitality. However, whether the dramatic consequences of their loss are due to their role as an old experienced figure or to their alpha status remains unclear. In a retrospective study, we tested that in a semi-free ranging colony of rhesus macaques (Macaca mulatta), the removal of a non-alpha matriarch, who had a large set of kin, led to changes in behavior and physiological stress within her matriline. Following her removal, her matriline increased in aggression, vigilance, and social grooming. Additionally, hierarchical stability, measured by levels of rank changes, decreased within her matriline, and levels of intense aggression by high-ranking animals were more frequent, as well as matrilineal wounding. Although ordinal rank was positively associated with higher chronic hair cortisol concentrations (HCCs) in the months before the matriarch’s removal, following her removal, only those who experienced large increases in rank within her matriline displayed higher HCCs. Changes in matrilineal stability, aggression, behavior, and HCCs within the other two matrilines in the troop were not evident, although caution is needed due to the small sample sizes. We conclude that the removal of the non-alpha matriarch led to matrilineal instability, characterized by higher levels of aggression and subsequent vigilance, rank changes, physiological stress, and grooming. We suggest that non-alpha matriarchs with a large number of kin and social support can be integral to the stability of matrilines.Division of Intramural Research, National Institute of Child Health and Human Development, 1ZIAHD001107- 3

Psychopharmacology drugs, the brain, and behavior

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