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issn:0018-506
1.  Androgenic anabolic steroid exposure during adolescence: Ramifications for brain development and behavior 
Hormones and behavior  2012;64(2):350-356.
Puberty is a critical period for brain maturation that is highly dependent on gonadal sex hormones. Modifications in the gonadal steroid environment, via the use of anabolic androgenic steroids (AAS), have been shown to affect brain development and behavior. Studies in both humans and animal models indicate that AAS exposure during adolescence alters normal brain remodeling, including structural changes and neurotransmitter function. The most commonly reported behavioral effect is an increase in aggression. Evidence has been presented to identify factors that influence the effect of AAS on the expression of aggression. The chemical composition of the AAS plays a major role in determining whether aggression is displayed, with testosterone being the most effective. The hormonal context, the environmental context, physical provocation and the perceived threat during the social encounter have all been found to influence the expression of aggression and sexual behavior. All of these factors point toward an altered behavioral state that includes an increased readiness to respond to a social encounter with heightened vigilance, and enhanced motivation. This AAS-induced state may be defined as emboldenment. The evidence suggests that the use of AAS during this critical period of development may increase the risk for maladaptive behaviors along with neurological disorders.
doi:10.1016/j.yhbeh.2012.12.009
PMCID: PMC3633688  PMID: 23274699
Testosterone; adolescence; HPG; aggression; sex behavior; plasticity
2.  Enduring influence of pubertal stressors on behavioral response to hormones in female mice 
Hormones and behavior  2013;64(2):390-398.
The pubertal period is a time of change in an animal’s response to stress, and it is a second period of sexual differentiation of the brain. Recently, it was discovered that particular stressors during the prolonged pubertal period of female mice result in enduring changes in behavioral responsiveness of the brain to estradiol and progesterone. Depending on the behavior, pubertal immune challenge or shipping from suppliers may decrease, eliminate, or even reverse the effects of estradiol. Pubertal immune challenge results in changes in the number of estrogen receptor-immunoreactive cells in key brain areas suggesting a cellular mechanism for this remodeling of the brain’s response to hormones. A hypothesis is put forward that predicts that particular adverse experiences in girls may cause long-term alterations in the brain’s response to estradiol and/or progesterone via activation of the immune system. This could lead to mood disorders or altered response to any behavior influenced by estradiol in humans.
doi:10.1016/j.yhbeh.2013.01.015
PMCID: PMC3761225  PMID: 23998680
Stress; Immune Challenge; Lipopolysaccharide; Depression; Anxiety; Cognitive function; Sexual behavior; Estradiol; Progesterone; Puberty; Females; Mood disorders
3.  Puberty and Gonadal Hormones: Role in Adolescent-typical Behavioral Alterations 
Hormones and behavior  2013;64(2):343-349.
Adolescence is characterized by a variety of behavioral alterations, including elevations in novelty-seeking and experimentation with alcohol and other drugs of abuse. Some adolescent-typical neurobehavioral alterations may depend upon pubertal rises in gonadal hormones, whereas others may be unrelated to puberty. Using a variety of approaches, studies in laboratory animals have not revealed clear relationships between pubertal-related changes and adolescent- or adult-typical behaviors that are not strongly sexually dimorphic. Data reviewed suggest surprisingly modest influences of gonadal hormones on alcohol intake, alcohol preference and novelty-directed behaviors. Gonadectomy in males (but not females) increased ethanol intake in adulthood following surgery either pre-pubertally or in adulthood, with these increases in intake largely reversed by testosterone replacement in adulthood, supporting an activational role of androgens in moderating ethanol intake in males. In contrast, neither pre-pubertal nor adult gonadectomy influenced sensitivity to the social inhibitory or aversive effects of ethanol when indexed via conditioned taste aversions, although gonadectomy at either age altered the microstructure of social behavior of both males and females. Unexpectedly, the pre-pubertal surgical manipulation process itself was found to increase later ethanol intake, decrease sensitivity to ethanol’s social inhibitory effects, attenuate novelty-directed behavior and lower social motivation, with gonadal hormones being necessary for these long-lasting effects of early surgical perturbations.
doi:10.1016/j.yhbeh.2012.11.012
PMCID: PMC3761212  PMID: 23998677
adolescence; alcohol; gonadal hormones; novelty; puberty; social behavior; stress; testosterone
4.  Puberty and Adolescent Sexuality 
Hormones and behavior  2013;64(2):280-287.
doi:10.1016/j.yhbeh.2013.03.007
PMCID: PMC3761219  PMID: 23998672
5.  Puberty as a Critical Risk Period for Eating Disorders: A Review of Human and Animal Studies 
Hormones and behavior  2013;64(2):399-410.
Puberty is one of the most frequently discussed risk periods for the development of eating disorders. Prevailing theories propose environmentally mediated sources of risk arising from the psychosocial effects (e.g., increased body dissatisfaction, decreased self-esteem) of pubertal development in girls. However, recent research highlights the potential role of ovarian hormones in phenotypic and genetic risk for eating disorders during puberty. The goal of this paper is to review data from human and animal studies in support of puberty as a critical risk period for eating disorders and evaluate the evidence for hormonal contributions. Data are consistent in suggesting that both pubertal status and pubertal timing significantly impact risk for most eating disorders in girls, such that advanced pubertal development and early pubertal timing are associated with increased rates of eating disorders and their symptoms in both cross-sectional and longitudinal research. Findings in boys have been much less consistent and suggest a smaller role for puberty in risk for eating disorders in boys. Twin and animal studies indicate that at least part of the female-specific risk is due to genetic factors associated with estrogen activation at puberty. In conclusion, data thus far support a role for puberty in risk for eating disorders and highlight the need for additional human and animal studies of hormonal and genetic risk for eating disorders during puberty.
doi:10.1016/j.yhbeh.2013.02.019
PMCID: PMC3761220  PMID: 23998681
puberty; eating disorders; anorexia nervosa; bulimia nervosa; ovarian hormones; estrogen; twin studies
6.  Fear learning and memory across adolescent development Hormones and Behavior Special Issue: Puberty and Adolescence 
Hormones and behavior  2013;64(2):380-389.
Throughout the past several decades, studies have uncovered a wealth of information about the neural circuitry underlying fear learning and extinction that has helped to inform treatments for fear-related disorders such as post-traumatic stress and anxiety. Yet, up to 40 percent of people do not respond to such treatments. Adolescence, in particular, is a developmental stage during which anxiety disorders peak, yet little is known about the development of fear-related neural circuitry during this period. Moreover, pharmacological and behavioral therapies that have been developed are based on mature circuitry and function. Here, we review neural circuitry implicated in fear learning and data from adolescent mouse and human fear learning studies. In addition, we propose a developmental model of fear neural circuitry that may optimize current treatments and inform when, during development, specific treatments for anxiety may be most effective.
doi:10.1016/j.yhbeh.2013.01.016
PMCID: PMC3761221  PMID: 23998679
Adolescence; Development; Fear; Extinction; Anxiety; Amygdala; Hippocampus; Prefrontal Cortex; Sensitive Period
8.  Environmental and social influences on neuroendocrine puberty and behavior in macaques and other nonhuman primates 
Hormones and behavior  2013;64(2):226-239.
Puberty is the developmental period when the hypothalamic-pituitary-gonadal (HPG) axis is activated, following a juvenile quiescent period, and reproductive capacity matures. Although pubertal events occur in a consistent sequence, there is considerable variation between individuals in the onset and timing of pubertal events, with puberty onset occurring earlier in girls than in boys. Evidence in humans demonstrates that social and environmental context influences the timing of puberty onset and may account for some of the observed variation. This review analyzes the nonhuman primate literature, focusing primarily on rhesus macaques (Macaca mulatta), to examine the social and environmental influences on puberty onset, how these factors influence puberty in males and females, and to review the relationship between puberty onset of adult neuroendocrine function and sexual behavior. Social and environmental factors influence the timing of puberty onset and pubertal events in nonhuman primates, as in humans, and the influences of these factors differ for males and females. In nonhuman primates, gonadal hormones are not required for sexual behavior, but modulate the frequency of occurrence of behavior, with social context influencing the relationship between gonadal hormones and sexual behavior. Thus, the onset of sexual behavior is independent of neuroendocrine changes at puberty; however, there are distinct behavioral changes that occur at puberty, which are modulated by social context. Puberty is possibly the developmental period when hormonal modulation of sexual behavior is organized, and thus, when social context interacts with hormonal state to strongly influence the expression of sexual behavior.
doi:10.1016/j.yhbeh.2013.05.003
PMCID: PMC3762264  PMID: 23998667
Puberty onset; Social influence; Environmental influence; Sex differences; Nonhuman primate; Sexual behavior
9.  The Amygdala: An Agent of Change in Adolescent Neural Networks 
Hormones and behavior  2013;64(2):298-313.
A unique component of adolescent development is the need to master new developmental tasks in which peer interactions become primary (for the purposes of becoming autonomous from parents, forming intimate friendships, and romantic/sexual partnerships). Previously, it has been suggested that the ability to master these tasks requires an important re-organization in the relation between perceptual, motivational, affective, and cognitive systems in a very general and broad way that is fundamentally influenced by the infusion of sex hormones during pubertal development (Scherf et al., 2012). Herein, we extend this argument to suggest that the amygdala, which is vastly connected with cortical and subcortical regions and contains sex hormone receptors, may lie at the heart of this re-organization. We propose that during adolescent development there is a shift in the attribution of relevance to existing stimuli and contexts that is mediated by the amygdala (e.g., heightened relevance of peer faces, reduced relevance of physical distance from parents). As a result, amygdala inputs to existing stable neural networks are re-weighted (increased or decreased), which destabilizes the functional interactions among regions within these networks and allows for a critical restructuring of the network functional organization. This process of network re-organization enables processing of qualitatively new kinds of social information and the emergence of novel behaviors that support mastery of adolescent-specific developmental tasks.
doi:10.1016/j.yhbeh.2013.05.011
PMCID: PMC3781589  PMID: 23756154
adolescence; neural networks; developmental tasks; pubertal development; brain development; amygdala; fusiform gyrus; face processing; fear learning; striatum; vmPFC; stress
10.  The Value of Comparative Approaches to our Understanding of Puberty as Illustrated by Investigations in Birds and Reptiles 
Hormones and behavior  2013;64(2):10.1016/j.yhbeh.2013.05.002.
Studies of birds and reptiles have provided many basic insights into the neuroendocrine control of reproductive processes. This research has elucidated mechanisms regulating both early development, including sexual differentiation, and adult neuroendocrine function and behavior. However, phenomena associated with the transition into sexual maturation (puberty) have not been a focus of investigators working on species in these taxonomic classes. Research is complicated in birds and reptiles by a variety of factors, including what can be extended times to maturation, the need to reach particular body size regardless of age, and environmental conditions that can support or inhibit endocrine responses. However, careful selection of model systems, particularly those with available genetic tools, will lead to important comparative studies that can elucidate both generalizability and diversity of mechanisms regulating the onset of reproductive maturity.
doi:10.1016/j.yhbeh.2013.05.002
PMCID: PMC3808991  PMID: 23998665
gonadotropin releasing hormone; kisspeptin; sexual maturation; photoperiodism; seasonal reproduction; Taeniopygia guttata; Anolis carolinensis
11.  A System Biology Approach to Identify Regulatory Pathways Underlying the Neuroendocrine Control of Female Puberty in Rats and Nonhuman Primates 
Hormones and behavior  2013;64(2):175-186.
Puberty is a major developmental milestone controlled by the interaction of genetic factors and environmental cues of mostly metabolic and circadian nature. An increased pulsatile release of the decapeptide gonadotropin releasing hormone (GnRH) from hypothalamic neurosecretory neurons is required for both the initiation and progression of the pubertal process. This increase is brought about by coordinated changes that occur in neuronal and glial networks associated with GnRH neurons. These changes ultimately result in increased neuronal and glial stimulatory inputs to the GnRH neuronal network and a reduction of transsynaptic inhibitory influences. While some of the major players controlling pubertal GnRH secretion have been identified using gene-centric approaches, much less is known about the system-wide control of the overall process. Because the pubertal activation of GnRH release involves a diversity of cellular phenotypes, and a myriad of intracellular and cell-to-cell signaling molecules, it appears that the overall process is controlled by a highly coordinated and interactive regulatory system involving hundreds, if not thousands, of gene products. In this article we will discuss emerging evidence suggesting that these genes are arranged as functionally connected networks organized, both internally and across sub-networks, in a hierarchical fashion. According to this concept, the core of these networks is composed of transcriptional regulators that, by directing expression of downstream subordinate genes, provide both stability and coordination to the cellular networks involved in initiating the pubertal process. The integrative response of these gene networks to external inputs is postulated to be coordinated by epigenetic mechanisms.
doi:10.1016/j.yhbeh.2012.09.013
PMCID: PMC3933372  PMID: 23998662
Female puberty; hypothalamus; transcriptional regulation; gene networks; systems biology; neuroendocrine control; neurotransmission; glial-neuronal communication
12.  The Development of Psychotic Disorders in Adolescence: A potential role for hormones 
Hormones and behavior  2013;64(2):411-419.
The notion that adolescence is characterized by dramatic changes in behavior, and often by emotional upheaval, is widespread and longstanding in popular western culture. In recent decades, this notion has gained increasing support from empirical research showing that the peri- and post-pubertal developmental stages are associated with a significant rise in the rate of psychiatric symptoms and syndromes. As a result, interest in adolescent development has burgeoned among researchers focused on the origins of schizophrenia and other psychotic disorders. Two factors have fueled this trend: 1) increasing evidence from longitudinal research that adolescence is the modal period for the emergence of “prodromal” manifestations, or precursors of psychotic symptoms, and 2) the rapidly accumulating scientific findings on brain structural and functional changes occurring during adolescence and young adulthood. Further, gonadal and adrenal hormones are beginning to play a more prominent role in conceptualizations of adolescent brain development, as well as in the origins of psychiatric symptoms during this period (Walker and Bollini, 2002; Walker et al., 2008). In this paper, we begin by providing an overview of the nature and course of psychotic disorders during adolescence/young adulthood. We then turn to the role of hormones in modulating normal brain development, and the potential role they might play in the abnormal brain changes that characterize youth at clinical high-risk (CHR) for psychosis. The activational and organizational effects of hormones are explored, with a focus on how hormone-induced changes might be linked with neuropathological processes in the emergence of psychosis.
doi:10.1016/j.yhbeh.2013.02.018
PMCID: PMC4070947  PMID: 23998682
psychosis; prodrome; puberty; adolescence; hypothalamic-pituitary-adrenal [HPA] axis; hypothalamic-pituitary-gonadal [HPG] axis; brain development
13.  Modulation of the arcuate nucleus-medial preoptic nucleus lordosis regulating circuit: a role for GABAB receptors 
Hormones and behavior  2013;64(1):136-143.
Estradiol rapidly activates a microcircuit in the arcuate nucleus of the hypothalamus (ARH) that is needed for maximal female sexual receptivity. Membrane estrogen receptor-α complexes with and signals through the metabotropic glutamate receptor-1a stimulating NPY release within the ARH activating proopiomelanocortin (POMC) neurons. These POMC neurons project to the medial preoptic nucleus (MPN) and release β-endorphin. Estradiol treatment induces activation/internalization of MPN μ-opioid receptors (MOR) to inhibit lordosis. Estradiol membrane action modulates ARH gamma-aminobutyric acid receptor-B (GABAB) activity. We tested the hypothesis that ARH GABAB receptors mediate estradiol-induced MOR activation and facilitation of sexual receptivity. Double label immunohistochemistry revealed expression of GABAB receptors in NPY, ERα and POMC expressing ARH neurons. Approximately 70% of POMC neurons expressed GABAB receptors. Because estradiol initially activates an inhibitory circuit and maintains activation of this circuit, the effects of blocking GABAB receptors were evaluated before estradiol benzoate (EB) treatment and after at the time of lordosis testing. Bilateral infusions of the GABAB receptor antagonist, CGP52432, into the ARH prior to EB treatment of ovariectomized rats prevented estradiol-induced activation/internalization of MPN MOR, and the rats remained unreceptive. However, in EB treated rats, bilateral CGP52432 infusions 30 minutes before behavior testing attenuated MOR internalization and facilitated lordosis. These results indicated that GABAB receptors were located within the lordosis-regulating ARH microcircuit and are necessary for activation and maintenance of the estradiol inhibition of lordosis behavior. Although GABAB receptors positively influence estradiol signaling, they negatively regulate lordosis behavior since GABAB activity maintains the estradiol-induced inhibition.
doi:10.1016/j.yhbeh.2013.06.001
PMCID: PMC3742545  PMID: 23756153
lordosis behavior; μ-opioid receptor
14.  On the value of seasonal mammals for identifying mechanisms underlying the control of food intake and body weight 
Hormones and Behavior  2014;66(1):56-65.
This article is part of a Special Issue “Energy Balance”.
Seasonal cycles of adiposity and body weight reflecting changes in both food intake and energy expenditure are the norm in mammals that have evolved in temperate and polar habitats. Innate circannual rhythmicity and direct responses to the annual change in photoperiod combine to ensure that behavior and energy metabolism are regulated in anticipation of altered energetic demands such as the energetically costly processes of hibernation, migration, and lactation. In the last decade, major progress has been made into identifying the central mechanisms that underlie these profound long-term changes in behavior and physiology. Surprisingly they are distinct from the peptidergic and aminergic systems in the hypothalamus that have been identified in studies of the laboratory mouse and rat and implicated in timing meal intervals and in short-term responses to caloric restriction. Comparative studies across rodents, ungulates and birds reveal that tanycytes embedded in the ependymal layer of the third ventricle play a critical role in seasonal changes because they regulate the local availability of thyroid hormone. Understanding how this altered hormonal environment might regulate neurogenesis and plasticity in the hypothalamus should provide new insight into development of strategies to manage appetite and body weight.
Highlights
•Seasonal cycles reveal novel mechanisms underlying control of food intake.•Hypothalamic tanycytes control seasonal changes in ingestive behavior.•Tanycytes regulate thyroid hormone transport and availability in the hypothalamus.•Thyroid hormone may regulate mechanisms important in initial development.•The adult seasonal hypothalamus is a region of structural and functional plasticity.
doi:10.1016/j.yhbeh.2014.03.009
PMCID: PMC4064697  PMID: 24681216
Appetite; Food intake; Body weight; Thyroid hormone; Season; Photoperiod
15.  What's In a Name? Considerations of Homologies and Nomenclature for Vertebrate Social Behavior Networks 
Hormones and behavior  2013;64(1):103-112.
Behavioral neuroendocrinology is an integrative discipline that spans a wide range of taxa and neural systems, and thus the appropriate designation of homology (sameness) across taxa is critical for clear communication and extrapolation of findings from one taxon to another. In the present review we address issues of homology that relate to neural circuits of social behavior and associated systems that mediate reward and aversion. We first address a variety of issues related to the so-called "social behavior network" (SBN), including homologies that are only partial (e.g., whereas the preoptic area of fish and amphibians contains the major vasopressin-oxytocin cell groups, these populations lie in the hypothalamus of other vertebrates). We also discuss recent evidence that clarifies anterior hypothalamus and periaqueductal gray homologies in birds. Finally, we discuss an expanded network model, the "social decision-making network" (SDM) which includes the mesolimbic dopamine system and other structures that provide an interface between the mesolimbic system and the SBN. This expanded model is strongly supported in mammals, based on a wide variety of evidence. However, it is not yet clear how readily the SDM can be applied as a pan-vertebrate model, given insufficient data on numerous proposed homologies and a lack of social behavior data for SDM components (beyond the SBN nodes) for amphibians, reptiles or fish. Functions of SDM components are also poorly known for birds. Nonetheless, we contend that the SDM model provides a very sound and important framework for the testing of many hypotheses in nonmammalian vertebrates.
doi:10.1016/j.yhbeh.2013.05.006
PMCID: PMC4038951  PMID: 23722238
16.  Individual variation in testosterone and parental care in a female songbird; the dark-eyed junco (Junco hyemalis) 
Hormones and behavior  2013;64(4):685-692.
Summary
When competition for sex-specific resources overlaps in time with offspring production and care, trade-offs can occur. Steroids hormones, particularly testosterone (T), play a crucial role in mediating such trade-offs in males, often increasing competitive behaviors while decreasing paternal behavior. Recent research has shown that females also face such trade-offs; however, we know little about the role of T in mediating female phenotypes in general, and the role of T in mediating trade-offs in females in particular. Here we examine the relationship between individual variation in maternal effort and endogenous T in the dark-eyed junco, a common songbird. Specifically, we measure circulating T before and after a physiological challenge (injection of gonadotropin releasing hormone, GnRH), and determine whether either measure is related to provisioning, brooding, or the amount of T sequestered in egg yolk. We found that females producing more T in response to a challenge spent less time brooding nestlings, but provisioned nestlings more frequently, and deposited more T in their eggs. These findings suggest that, while T is likely important in mediating maternal phenotypes and female life history tradeoffs, the direction of the relationships between T and phenotype may differ from what is generally observed in males, and that high levels of endogenous T are not necessarily as costly as previous work might suggest.
doi:10.1016/j.yhbeh.2013.09.002
PMCID: PMC4013145  PMID: 24060498
life history tradeoffs; endogenous steroids; testosterone; gonadotropin releasing hormone (GnRH); maternal care; yolk hormones; dark-eyed junco (Junco hyemalis)
17.  Social status modifies estradiol activation of sociosexual behavior in female rhesus monkeys 
Hormones and behavior  2012;62(5):612-620.
Estrogen (E2) has activational effects on sexual motivation and mitigating effects on anxiety-like behaviors that can be attenuated with chronic exposure to psychosocial stress. Some studies suggest that this attenuation can be overcome by higher doses of E2, while others show that chronic psychosocial stress may alter the mechanisms of E2 function, thus reducing any positive benefit from higher doses of E2. To determine the interaction between psychosocial stress and E2 dose on behavior, we examined the scope of attenuation across a suite of socioemotional behaviors, including reproduction, affiliation, aggression, submission, and anxiety-like behaviors on 36 ovariectomized female rhesus monkeys. Females were exposed to graded psychosocial stress, established by an intrinsic female dominance hierarchy, where subordinate animals receive high amounts of harassment. Our data show that E2 dose-dependently increased sexual motivation and male-affiliation in dominant (e.g. low-stress) females, while subordinate females showed no positive effects of E2, even at higher doses. In addition, contact aggression was attenuated in dominant females, while non-contact aggression was attenuated in both dominant and middle-ranking females. These results suggest that the stress-induced attenuation of E2's activational effects on sexual behavior and affiliation with males may not be overcome with higher doses of E2. Furthermore, the observed behavioral consequences of psychosocial stress and E2 dose may be dependent on the behaviors of all the females in the social-group, and better resolution on these effects depends on isolating treatment to individuals within the group to minimize alterations in social-group interactions.
doi:10.1016/j.yhbeh.2012.09.010
PMCID: PMC4010104  PMID: 23046624
estradiol; sexual behavior; affiliation; social subordination; rhesus monkeys
18.  Chemosignals, Hormones and Mammalian Reproduction 
Hormones and behavior  2013;63(5):723-741.
Many mammalian species use chemosignals to coordinate reproduction by altering the physiology and behavior of both sexes. Chemosignals prime reproductive physiology so that individuals become sexually mature and active at times when mating is most probable and suppress it when it is not. Once in reproductive condition, odors produced and deposited by both males and females are used to find and select individuals for mating. The production, dissemination and appropriate responses to these cues are modulated heavily by organizational and activational effects of gonadal sex steroids and thereby intrinsically link chemical communication to the broader reproductive context. Many compounds have been identified as “pheromones” but very few have met the expectations of that term: a unitary, species-typical substance that is both necessary and sufficient for an experience-independent behavioral or physiological response. In contrast, most responses to chemosignals are dependent or heavily modulated by experience, either in adulthood or during development. Mechanistically, chemosignals are perceived by both main and accessory (vomeronasal) olfactory systems with the importance of each system tied strongly to the nature of the stimulus rather than to the response. In the central nervous system, the vast majority of responses to chemosignals are mediated by cortical and medial amygdala connections with hypothalamic and other forebrain structures. Despite the importance of chemosignals in mammals, many details of chemical communication differ even among closely related species and defy clear categorization. Although generating much research and public interest, strong evidence for the existence of a robust chemical communication among humans is lacking.
doi:10.1016/j.yhbeh.2013.03.011
PMCID: PMC3667964  PMID: 23545474
Pheromone; Odor; Scent; Behavior; Physiology; Mammal; Olfactory; Vomeronasal; Sex; Sexual
19.  FRANK A. BEACH AWARD: Programming of Neuroendocrine Function by Early-Life Experience: A Critical Role for the Immune System 
Hormones and behavior  2013;63(5):684-691.
Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system, and several have a striking etiology in development as well. Our recent evidence using a rodent model of neonatal E. coli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood, and suggests that the early-life immune history of an individual may be critical to understanding the relative risk of developing later-life mental health disorders in humans. A single neonatal infection programs the function of immune cells within the brain, called microglia, for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits. I describe the important role of the immune system, notably microglia, during brain development, and discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, and cognition.
doi:10.1016/j.yhbeh.2013.02.017
PMCID: PMC3667966  PMID: 23474365
neonate; infection; microglia; development; learning; memory; Interleukin (IL)-1β; obesity; TLR4
20.  High rates of pregnancy loss by subordinates leads to high reproductive skew in wild golden lion tamarins (Leontopithecus rosalia) 
Hormones and behavior  2013;63(5):675-683.
Across taxa, cooperative breeding has been associated with high reproductive skew. Cooperatively breeding golden lion tamarins (Leontopithecus rosalia) were long thought to have a monogynous mating system in which reproduction was limited to a single dominant female. Subordinates with few reproductive opportunities delayed dispersal and remained in the natal group to provide alloparental care to siblings, thus allowing dominant reproductive females to meet the energetic needs associated with high rates of reproduction and successful infant rearing. The goal of this study was to re-assess monogyny in wild golden lion tamarin groups based upon pregnancy diagnoses that used non-invasive enzyme immunoassay for progesterone and cortisol, combined with weekly data on individual weight gain, bi-annual physical examinations noting pregnancy and lactation status and daily behavioral observations. We established quantitative and qualitative criteria to detect and determine the timing of pregnancies that did not result in the birth of infants. Pregnancy polygyny occurred in 83% of golden lion tamarin groups studied. The loss of 64% of subordinate pregnancies compared to only 15% by dominant females limited reproductive success mainly to dominant females, thus maintaining high reproductive skew in female golden lion tamarins. Pregnancy loss by subordinate adults did not appear to result from dominant interference in subordinate hormonal mechanisms, but more likely resulted from subordinate abandonment of newborn infants to mitigate dominant aggression.
doi:10.1016/j.yhbeh.2013.02.009
PMCID: PMC3667972  PMID: 23454002
cooperative breeding; reproductive skew; polygyny; reproductive suppression; pregnancy loss; dominant control; subordination; progesterone; cortisol; Leontopithecus rosalia
21.  DISTINCT BEHAVIORAL PHENOTYPES IN MALE MICE LACKING THE THYROID HORMONE RECEPTOR α1 OR β ISOFORMS 
Hormones and behavior  2013;63(5):742-751.
Thyroid hormones influence both neuronal development and anxiety via the thyroid hormone receptors (TRs). The TRs are encoded by two different genes, TRα and TRβ. The loss of TRα1 is implicated in increased anxiety in males, possibly via a hippocampal increase in GABAergic activity. We compared both social behaviors and two underlying and related non-social behaviors, state anxiety and responses to acoustic and tactile startle in the gonadally intact TRα1 knockout (α1KO) and TRβ (βKO) male mice to their wild-type counterparts. For the first time, we show an opposing effect of the two TR isoforms, TRα1 and TRβ, in the regulation of state anxiety, with α1 knockout animals (α1KO) showing higher levels of anxiety and βKO males showing less anxiety compared to respective wild-type mice. At odds with the increased anxiety in non-social environments, α1KO males also show lower levels of responsiveness to acoustic and tactile startle stimuli. Consistent with the data that T4 is inhibitory to lordosis in female mice, we show subtly increased sex behavior in α1KO male mice. These behaviors support the idea that TRα1 could be inhibitory to ERα driven transcription that ultimately impacts ERα driven behaviors such as lordosis. The behavioral phenotypes point to novel roles for the TRs, particularly in non-social behaviors such as state anxiety and startle.
doi:10.1016/j.yhbeh.2013.03.015
PMCID: PMC3726275  PMID: 23567476
thyroid hormone receptor; sexual behavior; arousal; anxiety
22.  Testosterone influences spatial strategy preferences among adult male rats 
Hormones and behavior  2013;63(5):800-812.
Males outperform females on some spatial tasks, and this may be partially due to the effects of sex steroids on spatial strategy preferences. Previous work with rodents indicates that low estradiol levels bias females toward a striatum-dependent response strategy, whereas high estradiol levels bias them toward a hippocampus-dependent place strategy. We tested whether testosterone influenced the strategy preferences in male rats. All subjects were castrated and assigned to one of three daily injection doses of testosterone (0.125, 0.250, or 0.500 mg/rat) or a control group that received daily injections of the drug vehicle. Three different maze protocols were used to determine rats’ strategy preferences. A low dose of testosterone (0.125 mg) biased males toward a motor-response strategy on a T-maze task. In a water maze task in which the platform itself could be used intermittently as a visual cue, a low testosterone dose (0.125 mg) caused a significant increase in the use of a cued-response strategy relative to control males. Results from this second experiment also indicated that males receiving a high dose of testosterone (0.500 mg) were biased toward a place strategy. A third experiment indicated that testosterone dose did not have a strong influence on the ability of rats to use a nearby visual cue (floating ball) in the water maze. For this experiment, all groups seemed to use a combination of place and cued-response strategies. Overall, the results indicate that the effects of testosterone on spatial strategy preference are dose dependent and task dependent.
doi:10.1016/j.yhbeh.2013.03.018
PMCID: PMC3759970  PMID: 23597827
Testosterone; Androgen; Spatial memory; Spatial strategy; Place strategy; Response strategy; Water maze; Radial arm maze; Rats
23.  Editorial comment: Oxytocin, vasopressin and social behavior 
Hormones and behavior  2012;61(3):227-229.
doi:10.1016/j.yhbeh.2012.02.019
PMCID: PMC4005251  PMID: 22443808
24.  INHIBITION OF GHRELIN O-ACYLTRANSFERASE ATTENUATES FOOD DEPRIVATION-INDUCED INCREASES IN INGESTIVE BEHAVIOR1 
Hormones and behavior  2013;63(4):667-673.
Ghrelin is an orexigenic hormone produced by the stomach in direct proportion to the time since the last meal and has therefore been called a ‘hunger signal’. The octanoylation of ghrelin is critical for its orexigenic functions and is dependent upon ghrelin O-acyltransferase (GOAT) catalyzation. The GOAT inhibitor, GO-CoA-Tat, decreases the circulating concentrations of octanoylated ghrelin and attenuates weight gain on a high fat diet in mice. Unlike rats and mice, Siberian hamsters and humans do not increase food intake after food deprivation, but increase food hoarding after food deprivation. In Siberian hamsters, exogenous ghrelin increases ingestive behaviors similarly to 48–56 h food deprivation. Therefore, we tested the necessity of increased ghrelin in food-deprived Siberian hamsters to stimulate ingestive behaviors. To do so we used our simulated natural housing system that allows hamsters to forage for and hoard food. Animals were given an injection of GO-CoA-Tat (i.p., 11 μmol/kg) every 6 h because that is the duration of its effective inhibition of octanoylated ghrelin concentrations during a 48 h food deprivation. We found that GO-CoA-Tat attenuated food foraging (0–1 h), food intake (0–1 and 2–4 h), and food hoarding (0–1 h and 2 and 3 d) post-refeeding compared with saline treated animals. This suggests that increased octanoylated ghrelin concentrations play a role in the food deprivation-induced increases in ingestive behavior. Therefore, ghrelin is a critical aspect of the multi-faceted mechanisms that stimulate ingestive behaviors, and might be a critical point for a successful clinical intervention scheme in humans.
doi:10.1016/j.yhbeh.2013.02.001
PMCID: PMC3633643  PMID: 23399323
hoarding; food intake; foraging; Siberian hamster; body mass
25.  The medial preoptic area is necessary for sexual odor preference, but not sexual solicitation, in female Syrian hamsters 
Hormones and behavior  2013;63(4):606-614.
Precopulatory behaviors that are preferentially directed towards opposite-sex conspecifics are critical for successful reproduction, particularly in species wherein the sexes live in isolation, such as Syrian hamsters (Mesocricetus auratus). In females, these behaviors include sexual odor preference and vaginal scent marking. The neural regulation of precopulatory behaviors is thought to involve a network of forebrain areas that includes the medial amygdala (MA), the bed nucleus of the stria terminalis (BNST), and the medial preoptic area (MPOA). Although MA and BNST are necessary for sexual odor preference and preferential vaginal marking to male odors, respectively, the role of MPOA in odor-guided female precopulatory behaviors is not well understood. To address this issue, female Syrian hamsters with bilateral, excitotoxic lesions of MPOA (MPOA-X) or sham lesions (SHAM) were tested for sexual odor investigation, scent marking, and lordosis. MPOA-X females did not investigate male odors more than female odors in an odor preference test, indicating that MPOA may be necessary for normal sexual odor preference in female hamsters. This loss of preference cannot be attributed to a sensory deficit, since MPOA-X females successfully discriminated male odors from female odors during an odor discrimination test. Surprisingly, no deficits in vaginal scent marking were observed in MPOA-X females, although these females did exhibit decreased overall levels of flank marking compared to SHAM females. Finally, all MPOA-X females exhibited lordosis appropriately. These results suggest that MPOA plays a critical role in the neural regulation of certain aspects of odor-guided precopulatory behaviors in female Syrian hamsters.
doi:10.1016/j.yhbeh.2013.02.003
PMCID: PMC3633686  PMID: 23415835
Olfaction; Chemosensory; Proceptive; Sexual motivation; Appetitive

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