ASU Scholarship Showcase

Illicit psychostimulant addiction remains a significant problem worldwide, despite decades of research into the neural underpinnings and various treatment approaches. The purpose of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in humans. Investigational pharmacological treatments for illicit psychostimulant addiction are also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs.

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats.

Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits.

Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation.

Human societies are unique in the level of cooperation among non-kin. Evolutionary models explaining this behavior typically assume pure strategies of cooperation and defection. Behavioral experiments, however, demonstrate that humans are typically conditional co-operators who have other-regarding preferences. Building on existing models on the evolution of cooperation and costly punishment, we use a utilitarian formulation of agent decision making to explore conditions that support the emergence of cooperative behavior. Our results indicate that cooperation levels are significantly lower for larger groups in contrast to the original pure strategy model. Here, defection behavior not only diminishes the public good, but also affects the expectations of group members leading conditional co-operators to change their strategies. Hence defection has a more damaging effect when decisions are based on expectations and not only pure strategies.

Attention deficit/hyperactivity disorder (ADHD) is a risk factor for tobacco use and dependence. This study examines the responsiveness to nicotine of an adolescent model of ADHD, the spontaneously hypertensive rat (SHR). The conditioned place preference (CPP) procedure was used to assess nicotine-induced locomotion and conditioned reward in SHR and the Wistar Kyoto (WKY) control strain over a range of nicotine doses (0.0, 0.1, 0.3 and 0.6 mg/kg). Prior to conditioning, SHRs were more active and less biased toward one side of the CPP chamber than WKY rats. Following conditioning, SHRs developed CPP to the highest dose of nicotine (0.6 mg/kg), whereas WKYs did not develop CPP to any nicotine dose tested. During conditioning, SHRs displayed greater locomotor activity in the nicotine-paired compartment than in the saline-paired compartment across conditioning trials. SHRs that received nicotine (0.1, 0.3, 0.6 mg/kg) in the nicotine-paired compartment showed an increase in locomotor activity between conditioning trials. Nicotine did not significantly affect WKY locomotor activity. These findings suggest that the SHR strain is a suitable model for studying ADHD-related nicotine use and dependence, but highlights potential limitations of the WKY control strain and the CPP procedure for modeling ADHD-related nicotine reward.

We present a phylogeographic study of at least six reproductively isolated lineages of new world harvester ants within the Pogonomyrmex barbatus and P. rugosus species group. The genetic and geographic relationships within this clade are complex: Four of the identified lineages show genetic caste determination (GCD) and are divided into two pairs. Each pair has evolved under a mutualistic system that necessitates sympatry. These paired lineages are dependent upon one another because their GCD requires interlineage matings for the production of F1 hybrid workers, and intralineage matings are required to produce queens. This GCD system maintains genetic isolation among these interdependent lineages, while simultaneously requiring co-expansion and emigration as their distributions have changed over time. It has also been demonstrated that three of these four GCD lineages have undergone historical hybridization, but the narrower sampling range of previous studies has left questions on the hybrid parentage, breadth, and age of these groups. Thus, reconstructing the phylogenetic and geographic history of this group allows us to evaluate past insights and hypotheses and to plan future inquiries in a more complete historical biogeographic context. Using mitochondrial DNA sequences sampled across most of the morphospecies’ ranges in the U.S.A. and Mexico, we conducted a detailed phylogeographic study. Remarkably, our results indicate that one of the GCD lineage pairs has experienced a dramatic range expansion, despite the genetic load and fitness costs of the GCD system. Our analyses also reveal a complex pattern of vicariance and dispersal in Pogonomyrmex harvester ants that is largely concordant with models of late Miocene, Pliocene, and Pleistocene range shifts among various arid-adapted taxa in North America.

A major conundrum in evolution is that, despite natural selection, polymorphism is still omnipresent in nature: Numerous species exhibit multiple morphs, namely several abundant values of an important trait. Polymorphism is particularly prevalent in asymmetric traits, which are beneficial to their carrier in disruptive competitive interference but at the same time bear disadvantages in other aspects, such as greater mortality or lower fecundity. Here we focus on asymmetric traits in which a better competitor disperses fewer offspring in the absence of competition. We report a general pattern in which polymorphic populations emerge when disruptive selection increases: The stronger the selection, the greater the number of morphs that evolve. This pattern is general and is insensitive to the form of the fitness function. The pattern is somewhat counterintuitive since directional selection is excepted to sharpen the trait distribution and thereby reduce its diversity (but note that similar patterns were suggested in studies that demonstrated increased biodiversity as local selection increases in ecological communities). We explain the underlying mechanism in which stronger selection drives the population towards more competitive values of the trait, which in turn reduces the population density, thereby enabling lesser competitors to stably persist with reduced need to directly compete. Thus, we believe that the pattern is more general and may apply to asymmetric traits more broadly. This robust pattern suggests a comparative, unified explanation to a variety of polymorphic traits in nature.

Positive allosteric modulators (PAMs) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a diverse class of compounds that increase fast excitatory transmission in the brain. AMPA PAMs have been shown to facilitate long-term potentiation, strengthen communication between various cortical and subcortical regions, and some of these compounds increase the production and release of brain-derived neurotrophic factor (BDNF) in an activity-dependent manner. Through these mechanisms, AMPA PAMs have shown promise as broad spectrum pharmacotherapeutics in preclinical and clinical studies for various neurodegenerative and psychiatric disorders. In recent years, a small collection of preclinical animal studies has also shown that AMPA PAMs may have potential as pharmacotherapeutic adjuncts to extinction-based or cue-exposure therapies for the treatment of drug addiction. The present paper will review this preclinical literature, discuss novel data collected in our laboratory, and recommend future research directions for the possible development of AMPA PAMs as anti-addiction medications.

Background: Increasing our understanding of the factors affecting the severity of the 2009 A/H1N1 influenza pandemic in different regions of the world could lead to improved clinical practice and mitigation strategies for future influenza pandemics. Even though a number of studies have shed light into the risk factors associated with severe outcomes of 2009 A/H1N1 influenza infections in different populations (e.g., [1-5]), analyses of the determinants of mortality risk spanning multiple pandemic waves and geographic regions are scarce. Between-country differences in the mortality burden of the 2009 pandemic could be linked to differences in influenza case management, underlying population health, or intrinsic differences in disease transmission [6]. Additional studies elucidating the determinants of disease severity globally are warranted to guide prevention efforts in future influenza pandemics.

In Mexico, the 2009 A/H1N1 influenza pandemic was characterized by a three-wave pattern occurring in the spring, summer, and fall of 2009 with substantial geographical heterogeneity [7]. A recent study suggests that Mexico experienced high excess mortality burden during the 2009 A/H1N1 influenza pandemic relative to other countries [6]. However, an assessment of potential factors that contributed to the relatively high pandemic death toll in Mexico are lacking. Here, we fill this gap by analyzing a large series of laboratory-confirmed A/H1N1 influenza cases, hospitalizations, and deaths monitored by the Mexican Social Security medical system during April 1 through December 31, 2009 in Mexico. In particular, we quantify the association between disease severity, hospital admission delays, and neuraminidase inhibitor use by demographic characteristics, pandemic wave, and geographic regions of Mexico.

Methods: We analyzed a large series of laboratory-confirmed pandemic A/H1N1 influenza cases from a prospective surveillance system maintained by the Mexican Social Security system, April-December 2009. We considered a spectrum of disease severity encompassing outpatient visits, hospitalizations, and deaths, and recorded demographic and geographic information on individual patients. We assessed the impact of neuraminidase inhibitor treatment and hospital admission delay (≤ > 2 days after disease onset) on the risk of death by multivariate logistic regression.

Results: Approximately 50% of all A/H1N1-positive patients received antiviral medication during the Spring and Summer 2009 pandemic waves in Mexico while only 9% of A/H1N1 cases received antiviral medications during the fall wave (P < 0.0001). After adjustment for age, gender, and geography, antiviral treatment significantly reduced the risk of death (OR = 0.52 (95% CI: 0.30, 0.90)) while longer hospital admission delays increased the risk of death by 2.8-fold (95% CI: 2.25, 3.41).

Conclusions: Our findings underscore the potential impact of decreasing admission delays and increasing antiviral use to mitigate the mortality burden of future influenza pandemics.

Tree-like structures are ubiquitous in nature. In particular, neuronal axons and dendrites have tree-like geometries that mediate electrical signaling within and between cells. Electrical activity in neuronal trees is typically modeled using coupled cable equations on multi-compartment representations, where each compartment represents a small segment of the neuronal membrane. The geometry of each compartment is usually defined as a cylinder or, at best, a surface of revolution based on a linear approximation of the radial change in the neurite. The resulting geometry of the model neuron is coarse, with non-smooth or even discontinuous jumps at the boundaries between compartments. We propose a hyperbolic approximation to model the geometry of neurite compartments, a branched, multi-compartment extension, and a simple graphical approach to calculate steady-state solutions of an associated system of coupled cable equations. A simple case of transient solutions is also briefly discussed.

We formulate an in silico model of pathogen avoidance mechanism and investigate its impact on defensive behavioural measures (e.g., spontaneous social exclusions and distancing, crowd avoidance and voluntary vaccination adaptation). In particular, we use SIR(B)S (e.g., susceptible-infected-recovered with additional behavioural component) model to investigate the impact of homo-psychologicus aspects of epidemics. We focus on reactionary behavioural changes, which apply to both social distancing and voluntary vaccination participations. Our analyses reveal complex relationships between spontaneous and uncoordinated behavioural changes, the emergence of its contagion properties, and mitigation of infectious diseases. We find that the presence of effective behavioural changes can impede the persistence of disease. Furthermore, it was found that under perfect effective behavioural change, there are three regions in the response factor (e.g., imitation and/or reactionary) and behavioural scale factor (e.g., global/local) factors ρ–α behavioural space. Mainly, (1) disease is always endemic even in the presence of behavioural change, (2) behavioural-prevalence plasticity is observed and disease can sometimes be eradication, and (3) elimination of endemic disease under permanence of permanent behavioural change is achieved. These results suggest that preventive behavioural changes (e.g., non-pharmaceutical prophylactic measures, social distancing and exclusion, crowd avoidance) are influenced by individual differences in perception of risks and are a salient feature of epidemics. Additionally, these findings indicates that care needs to be taken when considering the effect of adaptive behavioural change in predicting the course of epidemics, and as well as the interpretation and development of the public health measures that account for spontaneous behavioural changes.