Behavioral Syndrome Research Articles

Memantine: New prospective in bipolar disorder treatment.

We review preclinical and clinical evidences strongly suggesting that memantine, an old drug currently approved for Alzheimer's dementia, is an effective treatment for acute mania and for the prevention of manic/hypomanic and depressive recurrences of manic-depressive illness. Lithium remains the first line for the treatment and prophylaxis of bipolar disorders, but currently available treatment alternatives for lithium resistant patients are of limited and/or questionable efficacy. Thus, research and development of more effective mood stabilizer drugs is a leading challenge for modern psychopharmacology. We have demonstrated that 21 d administration of imipramine causes a behavioural syndrome similar to a cycle of bipolar disorder, i.e., a mania followed by a depression, in rats. Indeed, such treatment causes a behavioural supersensitivity to dopamine D2 receptor agonists associated with an increase sexual activity and aggressivity (mania). The dopamine receptor sensitization is followed, after imipramine discontinuation, by an opposite phenomenon (dopamine receptor desensitization) and an increased immobility time (depression) in the forced swimming test of depression. Memantine blocks the development of the supersensitivity and the ensuing desensitization associated with the depressive like behavior. On the basis of these observations we have suggested the use of memantine in the treatment of mania and in the prophylaxis of bipolar disorders. To test this hypothesis we performed several naturalistic studies that showed an acute antimanic effect and a long-lasting and progressive mood-stabilizing action (at least 3 years), without clinically relevant side effects. To confirm the observations of our naturalistic trials we are now performing a randomized controlled clinical trial. Finally we described the studies reporting the efficacy of memantine in manic-like symptoms occurring in psychiatric disorders other than bipolar. A randomized controlled clinical trial is needed to confirm our naturalistic observations. We believe that this review presents enough pharmacological and clinical information to consider the administration of memantine in the treatment of bipolar disorders that no respond to standard mood stabilizers.

Psychosis and Paroxysmal Visions in the Lives of the Founders of World Religions

Back to table of contents Previous article Next article LettersFull AccessPsychosis and Paroxysmal Visions in the Lives of the Founders of World ReligionsPhilip T. Nicholson, J.D., M.S.P.H.Philip T. NicholsonSearch for more papers by this author, J.D., M.S.P.H.Published Online:1 Jan 2014https://doi.org/10.1176/appi.neuropsych.12120412AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: In a recent article, “The Role of Psychotic Disorders in Religious History Considered,” Murray, Cunningham, and Price1 propose the provocative hypothesis that Abraham, Moses, Jesus, and Paul suffered primary or mood disorder-associated psychotic symptoms and that these experiences inspired the beliefs and actions that eventually led to the formation of new religions. Without discounting that hypothesis, I suggest that their analysis would be strengthened, first, by enlarging the sample of religious innovators to include the founders of all of the world’s major religions, and, second, by taking into account, as a primary etiological factor, a specific type of paroxysmal vision described as a “white light,” or, alternatively, as light that appears sun-like, fire-like, or lightning-like. Figure 1 lists descriptions of white-light visions by founders of the world’s major religions.FIGURE 1. Light-Visions of the Founders of World ReligionsIn order for the visual field to be inundated with white flashes, paroxysmal discharges must be present at a central location in the visual system, most likely in the hippocampus and its adjacent temporal cortices, which would eclipse other vision-related signals. When hippocampal seizures stimulate the septum, this generates sensations that clearly qualify as “ecstatic.”2 Other paroxysmal symptoms are sometimes present: muscle tremors, physical collapse, loss of consciousness, and/or temporary residual dysfunction, such as inability to speak (Ezekiel) or temporary blindness (Paul). Some of these seizures erupted spontaneously, consistent with a diagnosis of epilepsy, but, in many cases they were self-induced by persons for whom there is no other evidence of epileptic vulnerability, persons who adopted a dissociative defense strategy of frequent and prolonged “empty-mind” meditation. If apparently “normal” individuals can learn to self-induce temporolimbic visionary paroxysms at will, and if, as a result, they experience the dramatic changes associated with interictal behavior syndrome, the question of accounting for their charismatic influence on others is no longer as problematical as is the case with the hypothesis of psychosis.The clues revealing that founders were adept at meditation are references to seeing visions of light-rings or visions of green or blue lights. I have published elsewhere a neurologically-grounded, reverse-engineering analysis of the characteristics of meditation-induced light-visions demonstrating how visions of green light-rings and blue mists are generated by slow-wave sleep rhythms.3 Activating sleep rhythms when cortical neurons are already hyperexcitable for some reason (e.g., sleep loss or depression) can trigger a shift to corticothalamic hypersynchrony with surprising ease.4 If meditators continue to focus on the visual field, corticothalamic hypersynchrony can drive emergence of paroxysmal discharges in the hippocampus.3Although psychosis may on occasion shape the thoughts, emotions, and behaviors of some religious innovators, the critical events that change the lives of world-historical founders of world religions, which inspire them to initiate new religious ideas and practices that instill awe in their audiences, are temporolimbic seizures that have distinctive visual and ecstatic aurae, seizures that can be self-induced by “normal” individuals. Readers interested in viewing video animations of meditation-induced visions and descriptions of visions provided by influential mystics can visit www.religiousvisionsoflight.com.Medical Writere-mail: [email protected]netReferences1 Murray ED, Cunningham MG, Price BH: The role of psychotic disorders in religious history considered. J Neuropsychiatry Clin Neurosci 2012; 24:410–426Link, Google Scholar2 Hughes JR: The idiosyncratic aspects of the epilepsy of Fyodor Dostoevsky. Epilepsy Behav 2005; 7:531–538Crossref, Medline, Google Scholar3 Nicholson PT: Meditation & Light Visions: A Neurological Analysis. CreateSpace; An Online Division of Amazon Books, 2010Google Scholar4 Steriade M, Contreras D: Spike-wave complexes and fast components of cortically-generated seizures, I: role of neocortex and thalamus. J Neurophysiol 1998; 80:1439–1455Crossref, Medline, Google Scholar5 Nicholson PT: The Soma Code, Part III: visions, myths, and drugs. The Electronic Journal of Vedic Studies 2002; 8:70–92Google Scholar FiguresReferencesCited byDetailsCited ByReligion and delusionCurrent Opinion in Psychology, Vol. 40 Volume 26Issue 1 Winter 2014Pages E13-E14 Metrics PDF download History Published online 1 January 2014 Published in print 1 January 2014

Residual correlations, and not individual properties, determine a nest defense boldness syndrome

Different behavioral traits often covary, forming a behavioral syndrome. It is poorly known whether this covariance occurs on the between-individual level and what its selective consequences are. We used repeated measures (N = 562 observation events) of individual tawny owl Strix aluco females (N = 237) to study the integrated effects of seasonal timing of reproduction and clutch size on boldness displayed during defense of their clutch, in relation to plumage coloration, including local recruit production as a selective force on these traits. Using a Bayesian multivariate mixed model, we quantified the covariances between these traits on phenotypic, residual, and between-individual level and used a structural equation modeling approach to test the significance of presumed causal relationship between these traits in an a priori hypothesized path. On the phenotypic level, boldness was determined through early timing of breeding and larger clutch size, and early breeding increased recruitment probability. However, this relationship was entirely due to residual covariances and was not present on the between-individual level. The low individual-level correlations did not constrain the capacity of the population to respond to evolution as quantified by average autonomy (a metric summarizing evolutionary constraint on multiple traits). In the tawny owl, the association between early breeding and bold behavior, which is favored by selection, is solely due to extrinsic, nonheritable factors. We conclude that phenotypic evidence is insufficient to demonstrate syndrome covariance.

An integrated understanding of the personality concepts in animal personality psychology and behavioral syndrome research

An integrated understanding of the personality concepts in animal personality psychology and behavioral syndrome research

Syndromes or Flexibility: Behavior during a Life History Transition of a Coral Reef Fish

The theory of behavioral syndromes focuses on quantifying variation in behavior within and among individual organisms and attempts to account for the maintenance of differences in behavior that occur in a consistent manner among individuals. Behavioral syndromes have potentially important ecological consequences (e.g. survivorship tradeoffs) and can be shaped by population dynamics through selective mortality. Here, we search for any evidence for consistency of behavior across situations in juveniles of a common damselfish, Pomacentrus amboinensis (Pomacentridae) at the transition between larval habitats in the plankton and juvenile habitats on the reef. Naïve fish leaving the pelagic phase to settle on reefs were caught by light traps and their behaviors observed using similar methods across three different situations (small aquaria, large aquaria, field setting); all of which represent low risk and well-sheltered environments. Seven behavioral traits were compared within and among individuals across situations to determine if consistent behavioral syndromes existed. No consistency was found in any single or combination of behavioral traits for individuals across all situations. We suggest that high behavioral flexibility is likely beneficial for newly-settled fish at this ontogenetic transition and it is possible that consistent behavioral syndromes are unlikely to emerge in juveniles until environmental experience is gained or certain combinations of behaviors are favored by selective mortality.

Does Female Personality Determine Mate Choice Through Sexual Cannibalism?

AbstractAnimal personalities (e.g. consistent across‐context behavioural differences between individuals) can lead to differences in mate choice. However, evidence for this link remains limited. Pre‐mating sexual cannibalism can be a behavioural syndrome (i.e. a suboptimal personality) in which adaptive female aggression towards heterospecific prey spills over on non‐adaptive aggression towards courting males, independently of the female mating or feeding status (i.e. the ‘aggressive spillover hypothesis’,ASH). On the other hand, sexual cannibalism can also be a form of mate choice by which females selectively kill or mate with males depending on the male phenotype. We introduce the hypothesis that the most aggressive females in the population will not only attack males more frequently, but will be less likely to impose sexual selection on males through sexual cannibalism. Assuming that in a field common garden experiment in which females were fedad libitumthe rate of weight gain by a female may reflect her voracity or aggressiveness, we show that in the cannibalistic burrowing wolf spiderLycosa hispanica(formerlyL. tarantula), voracity towards heterospecific prey predicts a female's tendency towards sexual cannibalism. Unmated females with higher weight gains were more cannibalistic and attacked males regardless of the male phenotype. On the other hand, females that were less voracious tended to be less cannibalistic, and when they did kill a male, they were selective, killing males in poorer condition and mating with those in better condition. Our results demonstrate that females with different phenotypes (growth rates) differently imposed selection on male condition, tentatively supporting the hypothesis that female aggression levels can spill over on sexual selection through sexual cannibalism.

Parental Care Syndromes in House Sparrows: Positive Covariance Between Provisioning and Defense Linked to Parent Identity

AbstractParents of many species provide multiple forms of care to their offspring. In many birds, parents often provision offspring with food and defend them from predators and/or nest‐site competitors. We tested how these two forms of parental care covary in a wild population of house sparrows (Passer domesticus). Using a behavioral reaction norm approach, we found that nestling provisioning exhibited between individual differences and positively covaried with a measure of nest defense: the propensity to attack a heterospecific nest box competitor, the European starling (Sturnis vulgaris). This result would seem to support parental investment theory and suggests that high‐provisioning parents have high‐value offspring, which they will defend more vigorously than low‐provisioning parents. In addition, we found that parents with nestlings that hatched earlier in the season and grew faster approached a model starling more frequently and tended to be more likely to strike the starling. However, we also found that although brood value explained significant variation in both nestling provisioning and nest defense, it did not eliminate the positive, between‐individual relationship between provisioning and defense. This suggests that some of the correlation between provisioning and defense is tied to individual identity and hence may be a behavioral syndrome in which differences between individuals in underlying attributes produce correlated behaviors.

Personality affects learning and trade-offs between private and social information in guppies, Poecilia reticulata

The acquisition of information such as the location and quality of food, mates or shelter is a key survival requirement for animals. Individuals can acquire information through personal experience (private information) or through observing and interacting with others (social information). Environmental spatial and temporal heterogeneity can mean that sometimes social information conflicts with private knowledge. We tested how personality affected the importance placed on public versus private information in wild female guppies when these two information sources came into conflict. We found that boldness and sociality affected decisions to use conflicting social and private information. Bolder females used social information to avoid competition and/or potential patch depletion, whereas highly social individuals preferred the presence of conspecifics over rich foraging opportunities. There was no evidence of a speed–accuracy trade-off in a spatial associative learning task; rather, bold female guppies learned both more quickly and more accurately than shy females. We found no evidence of a behavioural syndrome between boldness and sociality which is consistent with previous studies on this population.

Boldness is influenced by sublethal interactions with predators and is associated with successful harem infiltration in Madagascar hissing cockroaches

One of the contemporary challenges of the behavioral syndromes literature is to identify how individual variation in behavior is determined, and whether this variation impacts ecological success. Although variation in experience is an obvious potential driver of intraspecific behavioral variation, predicting the impact of experience on suites of correlated behavioral traits is less intuitive. Specifically, if experience impacts traits that shape individuals' success in multiple contexts (e.g., foraging and anti-predator behavior), then experience could generate cross-contextual performance trade-offs associated with behavioral spillover. In the present study, we explore how sublethal experience with predators impacts various aspects of male behavioral tendencies in the Madagascar hissing cockroach, Gromphadorhina portentosa. First, we found that males' activity level and boldness were correlated together in the form of a behavioral syndrome. Second, we found that repeated sublethal interactions with predators shifted male boldness but not activity level, thus suggesting that the syndrome's constituent traits can respond to experience at least semi-independently. Third, we discovered that although predator exposure only influenced boldness, we found that boldness was highly correlated with males' ability to obtain rewarding positions in the harems of rival males. Taken together, our data suggest (but do not yet confirm) that although sublethal exposure to predators influences only a narrow subset of male's behavioral tendencies, these effects could still have nonintuitive consequences for males' success in functionally dissimilar ecological contexts (i.e., social and sexual encounters).

Does male behavioral type correlate with species recognition and stress?

The persistence of gynogenetic organisms is an evolutionary paradox. An ideal system for examining the persistence of gynogens is the unisexual–bisexual mating complex of the unisexual Amazon molly (Poecilia formosa), and the bisexual, parent species, the sailfin molly (Poecilia latipinna) and the Atlantic molly (Poecilia mexicana). Insight into the maintenance of this mating complex might be enhanced by taking a more holistic view of male and female behavior through a behavioral syndrome framework. In this study, we examined whether male mate choice is part of a behavioral syndrome. We quantified behaviors related to activity, boldness, exploration, and sociability in male sailfin mollies, as well as their mate preference for conspecific females or the all-female species of Amazon mollies. In addition, we explored the relationship between behavioral type and cortisol (a fish stress hormone) production in male sailfin mollies. We found evidence for behavioral correlations in male sailfin mollies, but individual behavioral type was not correlated with their mate preference or stress hormone production. However, we did find differences in preexperience cortisol production related to male boldness behaviors. The lack of correlation between behavioral types, mate preference, and stress hormone production emphasizes that the nature of behavioral–hormonal interactions is complex. In summary, neither individual traits nor the behavioral types found here are adequate to explain the maintenance of this unisexual–bisexual mating system.

The effects of 17α-ethinyloestradiol on boldness and its relationship to decision making in male Siamese fighting fish

Behavioural syndromes have received much attention by behavioural ecologists in recent years. While the relationship between boldness across contexts and between boldness and aggression are frequently investigated, little is known about how these relationships might change because of environmental disturbances such as exposure to endocrine disrupters. 17α-ethinyloestradiol (EE2) is an oestrogen mimic that is prevalent in aquatic ecosystems worldwide and has severe, negative impacts on the behaviour and physiology of exposed organisms. To assess how EE2 affects boldness and decision making, male Siamese fighting fish, Betta splendens, received repeated trials of three boldness assays (novel environment, empty tank and novel object) and one decision-making assay (a dummy male and female presented simultaneously) before and after exposure to acute, nominal doses of EE2. A control group of males received the same number of trials but was not exposed to EE2. When subjects were unexposed, a behavioural syndrome was found for boldness across contexts. In addition, boldness was positively correlated with aggression in the decision-making context. EE2 exposure disrupted this behavioural syndrome. In summary, EE2 exposure reduced overall behavioural response in all contexts, disrupted the behavioural syndrome and reduced behavioural consistency. Thus, even nominal, short-term exposure to EE2 can have dramatic effects on multiple levels of behaviour and potentially generate severe fitness consequences on exposed aquatic species. This study provides the first evidence of a boldness–aggression syndrome in this species and demonstrates that pollution may negatively influence consistent individual differences in behaviour.

Behavior Problems in Children With Specific Language Impairment

We studied behavior in a group of children with specific language impairment in its 2 subtypes (expressive and mixed receptive/expressive). After exclusion of other psychiatric conditions, we evaluated 114 children of ages 2 to 7 years using language developmental tests and behavioral screening scales. Behavior problems appeared in 54% of the children. Withdrawn was the most frequently found syndrome in preschool children, whereas anxious/depressed and social problems were the most frequent in older children. The high frequency of behavioral syndromes in children with specific language impairment is remarkable and requires the awareness of primary attendants and specialists. Anxiety, depression, social isolation, and aggressive and rule-breaking behavior can obscure identification of the language impairment. Taking into account this relationship would improve the chances of a timely and appropriate intervention.

Behavioral Syndromes in Mild Cognitive Impairment and Alzheimer's Disease

Behavioral disturbances belong to the core symptoms of dementia and are also common in mild cognitive impairment (MCI). The identification of sets of symptoms is clinically interesting, as interventions targeting syndromes may be more effective than the management of individual symptoms. This study aimed to identify, describe, measure, and compare the fundamental behavioral syndromes that underlie the observed behavioral symptoms in MCI and Alzheimer's disease (AD). A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms in MCI and dementia was performed. The study population consisted of 270 MCI and 402 AD patients. Behavioral assessment was performed by means of Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI), and Cornell Scale for Depression in Dementia (CSDD). Principal components factor analysis with Direct Oblimin rotation was carried out on the MFS score ≥5, seven cluster scores of the Behave-AD and the total scores of the CMAI and the CSDD. We identified three factors explaining behavior in the MCI group: a depression, a psychosis, and an agitation syndrome. Similar factors were found in AD, but the order: an agitation, a depression, and a psychosis syndrome, respectively, and the structure differed slightly. Diurnal rhythm disturbances and frontal lobe symptoms loaded with the depression syndrome in MCI and in AD they loaded with the agitation syndrome. Behavioral syndromes correlated in AD, but not in MCI, and the prevalence and severity of the behavioral syndromes were higher in AD than in MCI, except for the severity of the depression syndrome. In both MCI and AD, three similar behavioral syndromes exist, but behavior in MCI is more dominated by a depression syndrome, while behavior in AD is more subject to an agitation syndrome.

Assessing Frontal Behavioral Syndromes and Cognitive Functions in Traumatic Brain Injury

This study examined the relationship between individual and family ratings on a measure of frontal behaviors using the Frontal Systems Behavior Scale (FrSBe). Additionally, this study investigated whether self-reported symptoms of frontal-lobe dysfunction correspond to neuropsychological performance, particularly those tests measuring executive functions. Thirty-three individuals with moderate-to-severe traumatic brain injury (TBI) and 19 healthy individuals completed the FrSBe and neuropsychological measures. Results indicated that the self-ratings of individuals’ apathy, disinhibition, and executive dysfunction significantly increased from before to after injury, as did the family members’ ratings, with no significant difference between the patients’ and family members’ reports for any of the three FrSBe subscales. Although individuals with TBI demonstrated impairments in neuropsychological measures, including measures of executive functioning, few significant correlations were found between the patients’ FrSBe ratings and measures of cognitive functioning. This suggests that information from the FrSBe may differ from information gathered during a cognitive evaluation and may enhance our understanding of the behavioral sequelae following TBI that may not be captured by neuropsychological assessment alone.

Interpopulation Variations in Behavioral Syndromes of a Jumping Spider from Insecticide‐Treated and Insecticide‐Free Orchards

AbstractVariations in environmental conditions can influence behavioral syndromes (correlated tendencies in behaviors), and understanding the factors that shape trait covariation is particularly relevant when species are challenged by environmental changes. We investigated how behavioral syndromes varied at extremes of a gradient of anthropogenic disturbance, using apple orchards with different histories of insecticidal applications as a model system. Eris militaris (Araneae: Salticidae) jumping spiders were sampled from an insecticide‐free orchard and an insecticide‐treated orchard from Southern Québec. Spiders were tested for activity, aggression, boldness, and voracity under standardized conditions. Behavioral syndrome structure was compared between the two populations using Bayesian multiresponse models and structural equation modeling. Syndrome structure differed significantly between the two populations. The insecticide‐free population showed evidence of a syndrome involving all measured traits, while only aggression, boldness and voracity were correlated in the insecticide‐treated population. The insecticide‐free population showed negative correlations between active and voracious behavioral types vs. aggressive and bold types while the insecticide‐treated population showed a negative correlation between aggression‐boldness and voracity. This research is a first step in investigating the impact of anthropogenic disturbances on behavioral syndromes and demonstrates that behavioral syndromes may vary with respect to insecticidal applications.

Heightened serotonin influences contest outcome and enhances expression of high-intensity aggressive behaviors

The outcome of behavioral interactions between organisms can have significant fitness implications. Therefore, it is of great theoretical and practical importance to understand the mechanisms that modify different agonistic behaviors. Changes in central monoamines, such as serotonin (5-HT), contribute to modifying the expression of aggressive encounters in both vertebrates and invertebrates. In several invertebrate groups, neural 5-HT has been linked to heightened aggression and conflict escalation. The male stalk-eyed fly (Teleopsis dalmanni) competes with conspecifics daily over access to resources such as food and mates. Because encounters escalate in a stereotypical manner, stalk-eyed flies provide an excellent model system to study behavioral syndromes. We hypothesized that noninvasive, pharmacological augmentation of brain 5-HT by administration of the precursor, 5-hydroxytryptophan (5-HTP), would increase stereotypic behavioral escalation and the probability of winning a conflict over food. Size-matched male 5-HTP-treated and untreated flies were placed in a forced-fight paradigm and their aggressive behaviors scored. Individuals with higher brain 5-HT levels had a markedly higher probability of winning the contests, displayed greater levels of high-intensity aggressive behaviors and fewer retreats. Pretreatment with 5-HTP did not significantly alter octopamine or tyramine, suggesting that central 5-HT may modulate aggression in these organisms and play a role in determining reproductive success and resource attainment.

Asymmetric dopamine loss differentially affects effort to maximize gain or minimize loss

BackgroundDopamine (DA) plays an important role in regulating effort expenditure for reward, but whether it is also involved in modulating effort to avoid punishment is not clear. Preference for approach towards rewarding stimuli or away from aversive stimuli is associated with asymmetric activation in anterior brain regions. Asymmetric DA signaling in subcortical-frontal circuits may therefore contribute to differentially energizing behavior towards approach or avoidance behavior. We tested this hypothesis in patients with Parkinson's disease (PD), characterized by asymmetric DA loss. MethodsPatients with greater DA deficit in the left (n = 20) or right (n = 19) hemisphere, performed a task that measures separately effort to approach (maximize gains) versus effort to avoid (minimize loss), on and off DA replacement therapy. ResultsWhen tested off medication, patients with relatively greater DA deficit in the left hemisphere showed greater approach deficit (less effort to increase gain than to avoid loss) whereas the opposite pattern of effort expenditure was demonstrated by patients with greater DA deficit in the right hemisphere. Performing the same task when medicated revealed increased willingness to expend effort, such that increased effort to maximize gain was associated left hemisphere improved DA function (reflected by reduced symptoms), while increased effort to avoid loss was related to right hemisphere improvement. ConclusionsThese results suggest that asymmetry of DA levels modulates the differential exertion of effort toward attaining rewards versus avoiding aversive consequences, providing new insights into understanding the underlying pathophysiology of behavioral syndromes such as apathy and impulsive-compulsive disorders.

Nonlinear Pharmacokinetics of (±)3,4-Methylenedioxymethamphetamine (MDMA) and Its Pharmacodynamic Consequences in the Rat

3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug that can cause severe and even fatal adverse effects. However, interest remains for its possible clinical applications in posttraumatic stress disorder and anxiety treatment. Preclinical studies to determine MDMA's safety are needed. We evaluated MDMA's pharmacokinetics and metabolism in male rats receiving 2.5, 5, and 10 mg/kg s.c. MDMA, and the associated pharmacodynamic consequences. Blood was collected via jugular catheter at 0, 0.5, 1, 2, 4, 6, 8, 16, and 24 hours, with simultaneous serotonin (5-HT) behavioral syndrome and core temperature monitoring. Plasma specimens were analyzed for MDMA and the metabolites (±)-3,4-dihydroxymethamphetamine (HHMA), (±)-4-hydroxy-3-methoxymethamphetamine (HMMA), and (±)-3,4-methylenedioxyamphetamine (MDA) by liquid chromatography-tandem mass spectrometry. After 2.5 mg/kg MDMA, mean MDMA Cmax was 164 ± 47.1 ng/ml, HHMA and HMMA were major metabolites, and <20% of MDMA was metabolized to MDA. After 5- and 10-mg/kg doses, MDMA areas under the curve (AUCs) were 3- and 10-fold greater than those after 2.5 mg/kg; HHMA and HMMA AUC values were relatively constant across doses; and MDA AUC values were greater than dose-proportional. Our data provide decisive in vivo evidence that MDMA and MDA display nonlinear accumulation via metabolic autoinhibition in the rat. Importantly, 5-HT syndrome severity correlated with MDMA concentrations (r = 0.8083; P < 0.0001) and core temperature correlated with MDA concentrations (r = 0.7595; P < 0.0001), suggesting that MDMA's behavioral and hyperthermic effects may involve distinct mechanisms. Given key similarities between MDMA pharmacokinetics in rats and humans, data from rats can be useful when provided at clinically relevant doses.

Development of boldness and docility in yellow-bellied marmots

Personality traits are important because they can affect individual survival as well as how a population may respond to environmental change. How these traits arise, whether they are maintained throughout ontogeny, and how environmental factors differentially affect them throughout life is poorly understood. Understanding these pathways is important for determining the function and evolution of animal personality. We examined the development of two commonly studied personality traits, boldness and docility, in a long-term study of yellow-bellied marmots, Marmota flaviventris. Using data collected between 2002 and 2011, we quantified the repeatability within three age groups (juveniles, yearlings and adults), the correlation between age classes, and the behavioural syndromes of these two traits within the three life stages. We quantified boldness through flight initiation distance (FID) tests, and we quantified docility through marmots’ response to being trapped. We found that boldness was repeatable only in yearlings, but docility was repeatable in all age classes. We also found that juvenile docility predicted later docility. We also found no behavioural syndrome between boldness and docility in any life stage. This suggests an adaptive hypothesis: that these personality traits develop independently and at potentially age-appropriate times. Thus, the development of personality traits may facilitate animal’s coping with age-dependent requirements and constraints.

The Architecture of the Pollen Hoarding Syndrome in Honey Bees: Implications for Understanding Social Evolution, Behavioral Syndromes, and Selective Breeding.

Social evolution has influenced every aspect of contemporary honey bee biology, but the details are difficult to reconstruct. The reproductive ground plan hypothesis of social evolution proposes that central regulators of the gonotropic cycle of solitary insects have been coopted to coordinate social complexity in honey bees, such as the division of labor among workers. The predicted trait associations between reproductive physiology and social behavior have been identified in the context of the pollen hoarding syndrome, a larger suite of interrelated traits. The genetic architecture of this syndrome is characterized by a partially overlapping genetic architecture with several consistent, pleiotropic QTL. Despite these central QTL and an integrated hormonal regulation, separate aspects of the pollen hoarding syndrome may evolve independently due to peripheral QTL and additionally segregating genetic variance. The characterization of the pollen hoarding syndrome has also demonstrated that this syndrome involves many non-behavioral traits, which may be the case for numerous "behavioral" syndromes. Furthermore, the genetic architecture of the pollen hoarding syndrome has implications for breeding programs for improving honey health and other desirable traits: If these traits are comparable to the pollen hoarding syndrome, consistent pleiotropic QTL will enable marker assisted selection, while sufficient additional genetic variation may permit the dissociation of trade-offs for efficient multiple trait selection.