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1.
Matern Child Nutr ; 19(4): e13523, 2023 10.
Article in English | MEDLINE | ID: mdl-37378454

ABSTRACT

Antenatal multiple micronutrient supplementation (MMS) is an intervention that can help reach three of the six global nutrition targets, either directly or indirectly: a reduction in low birth weight, stunting, and anaemia in women of reproductive age. To support global guideline development and national decision-making on investments into maternal nutrition, Nutrition International developed a modelling tool called the MMS cost-benefit tool to help users understand whether antenatal MMS is better value for money than iron and folic acid supplementation (IFAS) during pregnancy. The MMS cost-benefit tool can generate estimates on the potential health impact, budget impact, economic value, cost-effectiveness and benefit-cost ratio of investing in MMS compared to IFAS in LMICs. In the 33 countries with data included in the tool, the MMS cost-benefit tool shows that transitioning is expected to generate substantial health benefits in terms of morbidity and mortality averted and can be very cost-effective in multiple scenarios for these countries. The cost per DALY averted averages at US$ 23.61 and benefit-cost ratio ranges from US$ 41-US$ 1304: $1.0, which suggest MMS is good value for money compared with IFAS. With its user-friendly design, open access availability, and online data-driven analytics, the MMS cost-benefit tool can be a powerful resource for governments and nutrition partners seeking timely and evidence-based analyses to inform policy-decision and investments towards the scale-up of MMS for pregnant women globally.


Subject(s)
Dietary Supplements , Micronutrients , Nutrition Policy , Micronutrients/economics , Nutrition Policy/economics , Humans , Female , Pregnancy , Dietary Supplements/economics , Cost-Benefit Analysis , Treatment Outcome
2.
Horm Behav ; 142: 105172, 2022 06.
Article in English | MEDLINE | ID: mdl-35405411

ABSTRACT

Habit formation is thought to involve two parallel processes that are mediated by distinct neural substates: one that suppresses goal-directed behavior, and one that facilitates stimulus-response (S-R) learning, which underscores habitual behavior. In previous studies we showed that habitual responding emerges early during instrumental training in gonadally-intact female, compared to male, rats. The present study aimed to determine the role of ovarian hormones during instrumental acquisition in the transition from goal-directed to habitual behavior in female rats. Ovariectomized (OVX) female rats were given subcutaneous silastic capsules that released low levels of 17-ß estradiol (E2) to maintain estrogen receptor availability. Rats were assigned to one of three hormone treatment conditions: no additional hormone replacement (Control group), replacement with high E2 (High E2 group), or replacement with high E2 followed by progesterone (High E2 + P4 group). Hormone replacement occurred twice during acquisition to mimic natural hormone fluctuations. At test, the Control and High E2 groups demonstrated responding that was sensitive to devaluation by lithium chloride-induced illness, indicating goal-directed behavior. In contrast, the High E2 + P4 group exhibited a pattern of devaluation-insensitive, habitual responding, that suggested the suppression of goal-directed processes. In a follow-up experiment, similar procedures were conducted, however during acquisition, OVX rats were given cyclic high E2 plus medroxy-progesterone (MPA), a form of progesterone that does not metabolize to neuroactive metabolites. In this group, goal-directed behavior was observed. These data indicate that habit formation is not facilitated in low estrogen states, nor in the presence of cyclic high E2. However, cyclic high E2, together with progesterone during acquisition, appears to facilitate the early emergence of habitual responding. Furthermore, these data suggest that a neuroactive progesterone metabolite, like allopregnanolone, in combination with high cyclic E2, supports this phenomenon.


Subject(s)
Estrogens , Progesterone , Animals , Estradiol/pharmacology , Estrogens/pharmacology , Female , Habits , Humans , Male , Ovariectomy , Progesterone/pharmacology , Rats , Receptors, Estrogen
3.
Neurosci Lett ; 730: 135027, 2020 06 21.
Article in English | MEDLINE | ID: mdl-32437898

ABSTRACT

Multiple lines of evidence implicate the serotonin (5-HT) system in social function, including biomarker findings in autism spectrum disorder. In mice, knock-in of a rare Gly56Ala substitution in the serotonin transporter (SERT) causes elevated whole blood 5-HT levels, increased 5-HT clearance in the brain, and altered social and repetitive behavior. To further examine the molecular impact of this variant on social response, SERT Ala56 mutant mice and wildtype littermate controls were exposed to a social or non-social stimulus. We examined the differential activation of the prefrontal cortex, lateral amygdala, and medial amygdala, to social stimuli through RNA sequencing. Differentially expressed genes were enriched in axonal guidance signaling pathways, networks related to nervous system development and function, neurological and psychiatric disorders, and behavior. These identified pathways and networks may shed light on the molecular cascades underlying the impact of altered SERT function on social behavior.


Subject(s)
Autism Spectrum Disorder/metabolism , Brain/growth & development , Gene Expression/physiology , Neurons/metabolism , Serotonin Plasma Membrane Transport Proteins/genetics , Animals , Disease Models, Animal , Male , Mice , Serotonin/metabolism , Social Behavior
4.
J Nutr ; 149(7): 1222-1229, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31131412

ABSTRACT

BACKGROUND: Recent evidence has encouraged low- and middle-income countries to consider transitioning from long-standing iron and folic acid supplementation (IFA) to multiple micronutrient supplementation (MMS) during pregnancy; however, global guidance is limited. To facilitate national decision-making, a cost-effectiveness model to compare supplementation approaches was developed, and applied to Pakistan, India, and Bangladesh. OBJECTIVE: We evaluated the incremental cost-effectiveness of transitioning from IFA to MMS. METHODS: The effectiveness of IFA compared with MMS during pregnancy was compared using 8 health outcomes reported in 2 meta-analyses published in 2017 (Cochrane and The Lancet). Impacts on health outcomes were aggregated using disability-adjusted life years (DALYs). Costs included the supplements and their distribution through antenatal care. The incremental cost-effective ratio (ICER) for transitioning from IFA to MMS was calculated for each country under each meta-analysis scenario, and Monte Carlo simulations were applied to generate a measure of certainty around the results. RESULTS: The effectiveness of transitioning from IFA to MMS under the Cochrane scenario was smaller and less certain compared with The Lancet scenario. However, even under the Cochrane scenario, MMS would avert 4,391, 5,769, and 8,578 more DALYs than IFA per 100,000 pregnancies in Pakistan, India, and Bangladesh, respectively (62.6%, 76.8%, and 82.6% certainty). The ICER of transitioning from IFA to MMS was 41.54, 31.62, and 21.26 US dollars (USD 2016) per DALY averted, respectively. CONCLUSIONS: Despite discrepancies in the overall effect of MMS depending on the meta-analysis used, MMS is cost-effective and generates positive health outcomes for both infants and pregnant women. Whilst the effectiveness of MMS is sensitive to the prevalence of certain health outcomes under the conservative scenario (Cochrane), MMS nevertheless averts more DALYs than IFA with high certainty and should re-enter public health discussion in Pakistan, India, and Bangladesh.


Subject(s)
Cost-Benefit Analysis , Dietary Supplements , Folic Acid/administration & dosage , Iron/administration & dosage , Micronutrients/administration & dosage , Models, Theoretical , Adult , Asia , Female , Humans , Infant , Infant Mortality , Infant, Newborn , Pregnancy
5.
Autism Res ; 12(5): 732-743, 2019 05.
Article in English | MEDLINE | ID: mdl-30977597

ABSTRACT

The K-Cl cotransporter KCC2 is essential in the development of the "GABA switch" that produces a change in neuronal responses to GABA signaling from excitatory to inhibitory early in brain development, and alterations in this progression have previously been hypothesized to play a causal role in autism spectrum disorder (ASD). We investigated the KCC2b (Slc12a5) heterozygous knockout mouse using a battery of rodent behavioral tests relevant to core and comorbid ASD symptoms. Compared to wild-type littermates, KCC2+/- mice were normal in standard measures of locomotor activity, grooming and digging behaviors, and social, vocalization, and anxiety-like behaviors. However, KCC2+/- mice exhibited increased social dominance behaviors and increased amplitude of spontaneous postsynaptic currents in the medial prefrontal cortex (PFC) that were previously implicated in governing social hierarchy and dominance behaviors. Treatment of wild-type mouse brain slices with the KCC2 inhibitor VU0240511 increased the amplitude and frequency of excitatory postsynaptic currents, partially recapitulating the phenotype of KCC2+/- mice. These findings indicate that the activity of KCC2 plays a role in social dominance, in parallel with effects on PFC signaling, further suggesting that KCC2 function has some relevance to social behavior but without the breadth of impact on autism-like behavior suggested by previous studies. Further testing could assess whether KCC2 alters other circuits and whether additional factors such as environmental insults may precipitate autism-related behavioral phenotypes. Autism Research 2019, 12: 732-743. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: A mouse model of altered chloride transporter expression was used to look for a role in behaviors and brain function relevant to autism. There was an imbalance in signaling in the prefrontal cortex, and increased social dominance behavior, although other autism-related behaviors were not changed. These findings indicate that altered chloride transporter function affects prefrontal cortex function and social dominance without a broader impact on autism-like behaviors.


Subject(s)
Autistic Disorder/physiopathology , Behavior, Animal/physiology , Electrophysiological Phenomena/physiology , Neurons/physiology , Prefrontal Cortex/physiopathology , Social Dominance , Animals , Disease Models, Animal , Male , Mice , Mice, Knockout
6.
Br J Pharmacol ; 174(16): 2716-2738, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28585320

ABSTRACT

BACKGROUND AND PURPOSE: The psychostimulant cocaine induces complex molecular, cellular and behavioural responses as a consequence of inhibiting presynaptic dopamine, noradrenaline and 5-HT transporters. To elucidate 5-HT transporter (SERT)-specific contributions to cocaine action, we evaluated cocaine effects in the SERT Met172 knock-in mouse, which expresses a SERT coding substitution that eliminates high-affinity cocaine recognition. EXPERIMENTAL APPROACH: We measured the effects of SERT Met172 on cocaine antagonism of 5-HT re-uptake using ex vivo synaptosome preparations and in vivo microdialysis. We assessed SERT dependence of cocaine actions behaviourally through acute and chronic locomotor activation, sensitization, conditioned place preference (CPP) and oral cocaine consumption. We used c-Fos, quantitative RT-PCR and RNA sequencing methods for insights into cellular and molecular networks supporting SERT-dependent cocaine actions. KEY RESULTS: SERT Met172 mice demonstrated functional insensitivity for cocaine at SERT. Although they displayed wild-type levels of acute cocaine-induced hyperactivity or chronic sensitization, the pattern of acute motor activation was different, with a bias toward thigmotaxis. CPP was increased, and a time-dependent elevation in oral cocaine consumption was observed. SERT Met172 mice displayed relatively higher levels of neuronal activation in the hippocampus, piriform cortex and prelimbic cortex (PrL), accompanied by region-dependent changes in immediate early gene expression. Distinct SERT-dependent gene expression networks triggered by acute and chronic cocaine administration were identified, including PrL Akt and nucleus accumbens ERK1/2 signalling. CONCLUSION AND IMPLICATIONS: Our studies reveal distinct SERT contributions to cocaine action, reinforcing the possibility of targeting specific aspects of cocaine addiction by modulation of 5-HT signalling.


Subject(s)
Central Nervous System Stimulants/pharmacology , Cocaine-Related Disorders/metabolism , Cocaine/pharmacology , Serotonin Plasma Membrane Transport Proteins/metabolism , Serotonin/metabolism , Animals , Central Nervous System Stimulants/administration & dosage , Cocaine/administration & dosage , Conditioning, Psychological , Female , Hippocampus/metabolism , Male , Mice , Motor Activity , Neurons , Nucleus Accumbens/metabolism , Prefrontal Cortex/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Serotonin Plasma Membrane Transport Proteins/genetics
7.
Mol Autism ; 8: 30, 2017.
Article in English | MEDLINE | ID: mdl-28649315

ABSTRACT

BACKGROUND: People with fragile X syndrome (FXS) often have deficits in social behavior, and a substantial portion meet criteria for autism spectrum disorder. Though the genetic cause of FXS is known to be due to the silencing of FMR1, and the Fmr1 null mouse model representing this lesion has been extensively studied, the contributions of this gene and its protein product, FMRP, to social behavior are not well understood. METHODS: Fmr1 null mice and wildtype littermates were exposed to a social or non-social stimulus. In one experiment, subjects were assessed for expression of the inducible transcription factor c-Fos in response to the stimulus, to detect brain regions with social-specific activity. In a separate experiment, tissue was taken from those brain regions showing differential activity, and RNA sequencing was performed. RESULTS: Immunohistochemistry revealed a significantly greater number of c-Fos-positive cells in the lateral amygdala and medial amygdala in the brains of mice exposed to a social stimulus, compared to a non-social stimulus. In the prelimbic cortex, there was no significant effect of social stimulus; although the number of c-Fos-positive cells was lower in the social condition compared to the non-social condition, and negatively correlated with c-Fos in the amygdala. RNA sequencing revealed differentially expressed genes enriched for molecules known to interact with FMRP and also for autism-related genes identified in the Simons Foundation Autism Research Initiative gene database. Ingenuity Pathway Analysis detected enrichment of differentially expressed genes in networks and pathways related to neuronal development, intracellular signaling, and inflammatory response. CONCLUSIONS: Using the Fmr1 null mouse model of fragile X syndrome, we have identified brain regions, gene networks, and molecular pathways responsive to a social stimulus. These findings, and future experiments following up on the role of specific gene networks, may shed light on the neural mechanisms underlying dysregulated social behaviors in fragile X syndrome and more broadly.


Subject(s)
Amygdala/metabolism , Disease Models, Animal , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/genetics , Limbic Lobe/metabolism , Amygdala/physiopathology , Animals , Behavior, Animal , Biomarkers/analysis , Brain Mapping , Fragile X Mental Retardation Protein/metabolism , Fragile X Syndrome/diagnosis , Fragile X Syndrome/physiopathology , Gene Deletion , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Gene Regulatory Networks , Humans , Interpersonal Relations , Limbic Lobe/physiopathology , Male , Mice , Mice, Knockout , Molecular Sequence Annotation , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-fos/metabolism , Sequence Analysis, RNA , Signal Transduction
8.
Omega (Westport) ; 75(2): 124-150, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28490283

ABSTRACT

Human-animal relationships are increasingly incorporated into families as a normal part of family life. Despite this, relationships with animals are often viewed as inferior to human relationships. This becomes problematic during times of loss and grief when members of a grieving companion animal owner's support system do not understand the salience of the relationship with the animal. Veterinary and other helping professionals need basic information about the experience of companion animal loss in order to help support and normalize the experiences of grieving companion animal owners. The present study qualitatively describes human-animal relationships and the subsequent loss and coping experienced by owners of beloved companion animals. Comparison with human and other types of loss and factors unique to companion animal loss are discussed, and practical applications for veterinary and other helping professionals are provided.


Subject(s)
Adaptation, Psychological , Bereavement , Human-Animal Bond , Pets , Adult , Aged , Aged, 80 and over , Animals , Female , Humans , Interviews as Topic , Kansas , Male , Middle Aged , Nebraska
9.
Psychoneuroendocrinology ; 68: 156-62, 2016 06.
Article in English | MEDLINE | ID: mdl-26974500

ABSTRACT

The peptide hormone oxytocin (OT) plays an important role in social behaviors, including social bond formation. In different contexts, however, OT is also associated with aggression, social selectivity, and reduced affiliation. Female meadow voles form social preferences for familiar same-sex peers under short, winter-like day lengths in the laboratory, and provide a means of studying affiliation outside the context of reproductive pair bonds. Multiple lines of evidence suggest that the actions of OT in the lateral septum (LS) may decrease affiliative behavior, including greater density of OT receptors in the LS of meadow voles that huddle less. We infused OT into the LS of female meadow voles immediately prior to cohabitation with a social partner to determine its effects on partner preference formation. OT prevented the formation of preferences for the partner female. Co-administration of OT with a specific OT receptor antagonist did not reverse the effect, but co-administration of OT with a specific vasopressin 1a receptor (V1aR) antagonist did, indicating that OT in the LS likely acted through V1aRs to decrease partner preference. Receptor autoradiography revealed dense V1aR binding in the LS of female meadow voles. These results suggest that the LS is a brain region that may be responsible for inhibitory effects of OT administration on affiliation, which will be important to consider in therapeutic administrations of OT.


Subject(s)
Arvicolinae/physiology , Oxytocin/pharmacology , Receptors, Vasopressin/metabolism , Sexual Behavior, Animal/drug effects , Animals , Arvicolinae/metabolism , Arvicolinae/psychology , Autoradiography , Brain/drug effects , Female , Pair Bond , Peer Group , Receptors, Oxytocin/metabolism , Septal Nuclei/drug effects , Social Behavior
10.
Horm Behav ; 79: 52-7, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26777726

ABSTRACT

Affiliative social relationships are impacted by stressors and can shape responses to stress. However, the effects of stress on social relationships in different contexts are not well understood. Meadow voles provide an opportunity to study these effects on peer relationships outside of a reproductive context. In winter months, female meadow voles cohabit with peers of both sexes, and social huddling is facilitated by exposure to short, winter-like day lengths in the lab. We investigated the role of stress and corticosterone (cort) levels in social behavior in short day-housed female meadow voles. A brief forced swim elevated cort levels, and we assessed the effects of this stressor on new and established relationships between females. In pairs formed following exposure to swim stress, the stressor significantly reduced the fraction of huddling time subjects spent with a familiar partner. Swim stress did not affect partner preferences in pairs established prior to the stressor. Finally, we examined fecal glucocorticoid metabolite levels via immunoassay in voles housed under short day (10h light) versus long day (14 h light) conditions and detected higher glucocorticoid levels in long day-housed voles. These findings support a role for stress regulation in the formation of social relationships in female meadow voles, and are consistent with a potential role for seasonal variation in cort in the behavioral transition from solitary to social. Together they highlight the importance of stress and possibly glucocorticoid signaling for social behavior.


Subject(s)
Arvicolinae , Social Behavior , Stress, Psychological/psychology , Animals , Arvicolinae/psychology , Behavior, Animal/physiology , Corticosterone/metabolism , Female , Humans , Male , Mating Preference, Animal/physiology , Pair Bond , Seasons , Sexual Behavior/psychology , Stress, Psychological/physiopathology
11.
PLoS One ; 10(5): e0125225, 2015.
Article in English | MEDLINE | ID: mdl-25932952

ABSTRACT

Inflammatory bowel disease is a chronic gastrointestinal inflammatory disorder associated with changes in neuropeptide expression and function, including vasoactive intestinal peptide (VIP). VIP regulates intestinal vasomotor and secretomotor function and motility; however, VIP's role in development and maintenance of colonic epithelial barrier homeostasis is unclear. Using VIP deficient (VIPKO) mice, we investigated VIP's role in epithelial barrier homeostasis, and susceptibility to colitis. Colonic crypt morphology and epithelial barrier homeostasis were assessed in wildtype (WT) and VIPKO mice, at baseline. Colitic responses were evaluated following dinitrobenzene sulfonic acid (DNBS) or dextran-sodium sulfate (DSS) exposure. Mice were also treated with exogenous VIP. At baseline, VIPKO mice exhibited distorted colonic crypts, defects in epithelial cell proliferation and migration, increased apoptosis, and altered permeability. VIPKO mice also displayed reduced goblet cell numbers, and reduced expression of secreted goblet cell factors mucin 2 and trefoil factor 3. These changes were associated with reduced expression of caudal type homeobox 2 (Cdx2), a master regulator of intestinal function and homeostasis. DNBS and DSS-induced colitis were more severe in VIPKO than WT mice. VIP treatment rescued the phenotype, protecting VIPKO mice against DSS colitis, with results comparable to WT mice. In conclusion, VIP plays a crucial role in the development and maintenance of colonic epithelial barrier integrity under physiological conditions and promotes epithelial repair and homeostasis during colitis.


Subject(s)
Colitis/prevention & control , Homeostasis/drug effects , Intestines/pathology , Protective Agents/pharmacology , Vasoactive Intestinal Peptide/metabolism , Animals , CDX2 Transcription Factor , Cell Count , Colitis/pathology , Dinitrofluorobenzene/analogs & derivatives , Disease Susceptibility , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Goblet Cells/pathology , Homeodomain Proteins/metabolism , Intestines/drug effects , Male , Mice, Inbred C57BL , Mice, Knockout , Real-Time Polymerase Chain Reaction , Signal Transduction/drug effects , Transcription Factors/metabolism , Vasoactive Intestinal Peptide/deficiency
12.
Soc Neurosci ; 9(5): 484-94, 2014.
Article in English | MEDLINE | ID: mdl-24963825

ABSTRACT

Dominance hierarchies are an important aspect of group-living as they determine individual access to resources. The existence of dominance ranks in access to space has not been described in socially monogamous, communally nesting prairie voles (Microtus ochrogaster). Here, we tested whether dominance could be assessed using the tube test. We also tested whether dominance related to alcohol intake, similar to what has been demonstrated in nonmonogamous species. Same-sex pairs of unfamiliar peers were tested in a series of three trials of the tube test, then paired and allowed individual access to alcohol and water for 4 days, and then tested again in the tube test. For all pairs, the same subjects won the majority of trials before and after alcohol drinking. The number of wins negatively correlated with alcohol intake on the first day of drinking and positively correlated with levels of Fos in the paraventricular nucleus of the hypothalamus following the tube test in a separate group of voles. Dominance was not related to Fos levels in other brain regions examined. Together, these results indicate that prairie voles quickly establish stable dominance ranks through a process possibly involving the hypothalamus and suggest that dominance is linked to alcohol drinking.


Subject(s)
Alcohol Drinking/psychology , Arvicolinae/physiology , Paraventricular Hypothalamic Nucleus/physiology , Peer Group , Social Dominance , Aging , Alcohol Drinking/physiopathology , Animals , Arvicolinae/psychology , Body Weight , Central Nervous System Depressants/administration & dosage , Ethanol/administration & dosage , Female , Immunohistochemistry , Male , Oxytocin/metabolism , Paraventricular Hypothalamic Nucleus/drug effects , Proto-Oncogene Proteins c-fos/metabolism , Psychological Tests
13.
Proc Natl Acad Sci U S A ; 111(16): 6052-7, 2014 Apr 22.
Article in English | MEDLINE | ID: mdl-24711424

ABSTRACT

Alcohol use and abuse profoundly influences a variety of behaviors, including social interactions. In some cases, it erodes social relationships; in others, it facilitates sociality. Here, we show that voluntary alcohol consumption can inhibit male partner preference (PP) formation (a laboratory proxy for pair bonding) in socially monogamous prairie voles (Microtus ochrogaster). Conversely, female PP is not inhibited, and may be facilitated by alcohol. Behavior and neurochemical analysis suggests that the effects of alcohol on social bonding are mediated by neural mechanisms regulating pair bond formation and not alcohol's effects on mating, locomotor, or aggressive behaviors. Several neuropeptide systems involved in the regulation of social behavior (especially neuropeptide Y and corticotropin-releasing factor) are modulated by alcohol drinking during cohabitation. These findings provide the first evidence to our knowledge that alcohol has a direct impact on the neural systems involved in social bonding in a sex-specific manner, providing an opportunity to explore the mechanisms by which alcohol affects social relationships.


Subject(s)
Alcohol Drinking/physiopathology , Arvicolinae/physiology , Pair Bond , Sex Characteristics , Aggression , Animals , Female , Male , Mating Preference, Animal/physiology , Neuropeptides/metabolism , Proto-Oncogene Proteins c-fos/metabolism
14.
Front Behav Neurosci ; 7: 185, 2013 Dec 11.
Article in English | MEDLINE | ID: mdl-24376404

ABSTRACT

In recent decades, scientific understanding of the many roles of oxytocin (OT) in social behavior has advanced tremendously. The focus of this research has been on maternal attachments and reproductive pair-bonds, and much less is known about the substrates of sociality outside of reproductive contexts. It is now apparent that OT influences many aspects of social behavior including recognition, trust, empathy, and other components of the behavioral repertoire of social species. This review provides a comparative perspective on the contributions of OT to life in mammalian social groups. We provide background on the functions of OT in maternal attachments and the early social environment, and give an overview of the role of OT circuitry in support of different mating systems. We then introduce peer relationships in group-living rodents as a means for studying the importance of OT in non-reproductive affiliative behaviors. We review species differences in oxytocin receptor (OTR) distributions in solitary and group-living species of South American tuco-tucos and in African mole-rats, as well as singing mice. We discuss variation in OTR levels with seasonal changes in social behavior in female meadow voles, and the effects of OT manipulations on peer huddling behavior. Finally, we discuss avenues of promise for future investigation, and relate current findings to research in humans and non-human primates. There is growing evidence that OT is involved in social selectivity, including increases in aggression toward social outgroups and decreased huddling with unfamiliar individuals, which may support existing social structures or relationships at the expense of others. OT's effects reach beyond maternal attachment and pair bonds to play a role in affiliative behavior underlying "friendships", organization of broad social structures, and maintenance of established social relationships with individuals or groups.

15.
Front Pharmacol ; 4: 84, 2013.
Article in English | MEDLINE | ID: mdl-23847535

ABSTRACT

Peer influences are critical in the decrease of alcohol (ethanol) abuse and maintenance of abstinence. We previously developed an animal model of inhibitory peer influences on ethanol drinking using prairie voles and here sought to understand whether this influential behavior was due to specific changes in drinking patterns and to variation in a microsatellite sequence in the regulatory region of the vasopressin receptor 1a gene (avpr1a). Adult prairie voles' drinking patterns were monitored in a lickometer apparatus that recorded each lick a subject exhibited during continuous access to water and 10% ethanol during periods of isolation, pair housing of high and low drinkers, and subsequent isolation. Analysis of fluid consumption confirmed previous results that high drinkers typically decrease ethanol intake when paired with low drinkers, but that a subset of voles do not decrease. Analysis of bout structure revealed differences in the number of ethanol drinking bouts in the subpopulations of high drinkers when paired with low drinkers. Lickometer drinking patterns analyzed by visual and by cross-correlation analyses demonstrated that pair housing did not increase the rate of subjects drinking in bouts occurring at the same time. The length of the avpr1a microsatellite did not predict susceptibility to peer influence or any other drinking behaviors. In summary, subpopulations of high drinkers were identified, by fluid intake and number of drinking bouts, which did or did not lower their ethanol intake when paired with a low drinking peer, and these subpopulations should be explored for testing the efficacy of treatments to decrease ethanol use in groups that are likely to be responsive to different types of therapy.

16.
Peptides ; 40: 22-9, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23262357

ABSTRACT

Neuropeptide Y (NPY) has been implicated as a modulator of social behavior, often in a species-specific manner. Comparative studies of closely related vole species are particularly useful for identifying neural systems involved in social behaviors in both voles and humans. In the present study, immunohistochemistry was performed to compare NPY-like immunoreactivity (-ir) in brain tissue of the socially monogamous prairie vole and non-monogamous meadow vole. Species differences in NPY-ir were observed in a number of regions including the cortex, extended amygdala, septal area, suprachiasmatic nucleus, and intergeniculate leaf. Meadow voles had higher NPY-ir in all these regions as compared to prairie voles. No differences were observed in the striatum or hippocampus. The extended amygdala and lateral septum are regions that play a key role in regulation of monogamous behaviors such as pair bonding and paternal care. The present study suggests NPY in these regions may be an additional modulator of these species-specific social behaviors. Meadow voles had moderately higher NPY-ir in a number of hypothalamic regions, especially in the suprachiasmatic nucleus. Meadow voles also had much higher levels of NPY-ir in the intergeniculate leaflet, another key region in the regulation of circadian rhythms. Overall, species differences in NPY-ir were observed in a number of brain regions implicated in emotion, stress, circadian, and social behaviors. These findings provide additional support for a role for the NPY system in species-typical social behaviors.


Subject(s)
Amygdala/metabolism , Arginine Vasopressin/metabolism , Arvicolinae/metabolism , Brain/metabolism , Animals , Arvicolinae/physiology , Brain/physiology , Humans , Hypothalamus/metabolism , Immunohistochemistry , Social Behavior , Species Specificity
17.
J Vet Med Educ ; 39(4): 322-30, 2012.
Article in English | MEDLINE | ID: mdl-23187025

ABSTRACT

Mental health needs of veterinary medical students have become the focus of concern in recent years. Literature to date is scarce, but indicates a large number of veterinary medical students experience clinical levels of anxiety and depression. The present study focused on the prevalence of anxiety and depression in a sample of veterinary medical students (N=142) across four-year cohorts. Findings indicate elevated scores of anxiety and depression across the four-year cohorts. Students in their second and third years had the highest anxiety and depression scores. Perceived physical health, unclear expectations, difficulty fitting in, heavy workload, and homesickness were most relevant in explaining anxiety and depression symptom prevalence. Implications for practice and future research are addressed based on these findings.


Subject(s)
Anxiety/epidemiology , Depression/epidemiology , Mental Health , Schools, Veterinary , Stress, Psychological/epidemiology , Students, Medical/psychology , Adult , Anxiety/etiology , Cohort Studies , Depression/etiology , Female , Humans , Kansas/epidemiology , Male , Prevalence , Risk Factors , Surveys and Questionnaires , Young Adult
18.
J Vet Med Educ ; 39(4): 341-58, 2012.
Article in English | MEDLINE | ID: mdl-23187027

ABSTRACT

This study builds on previous research on predictors of depression and anxiety in veterinary medical students and reports data on three veterinary cohorts from two universities through their first three semesters of study. Across all three semesters, 49%, 65%, and 69% of the participants reported depression levels at or above the clinical cut-off, suggesting a remarkably high percentage of students experiencing significant levels of depression symptoms. Further, this study investigated the relationship between common stressors experienced by veterinary students and mental health, general health, and academic performance. A factor analysis revealed four factors among stressors common to veterinary students: academic stress, transitional stress, family-health stress, and relationship stress. The results indicated that both academic stress and transitional stress had a robust impact on veterinary medical students' well-being during their first three semesters of study. As well, academic stress negatively impacted students in the areas of depression and anxiety symptoms, life satisfaction, general health, perception of academic performance, and grade point average (GPA). Transitional stress predicted increased depression and anxiety symptoms and decreased life satisfaction. This study helped to further illuminate the magnitude of the problem of depression and anxiety symptoms in veterinary medical students and identified factors most predictive of poor outcomes in the areas of mental health, general health, and academic performance. The discussion provides recommendations for considering structural changes to veterinary educational curricula to reduce the magnitude of academic stressors. Concurrently, recommendations are suggested for mental health interventions to help increase students' resistance to environmental stressors.


Subject(s)
Anxiety/epidemiology , Depression/epidemiology , Education, Veterinary , Mental Health , Stress, Psychological/epidemiology , Students, Medical/psychology , Adult , Cohort Studies , Educational Measurement , Factor Analysis, Statistical , Female , Humans , Male , Midwestern United States/epidemiology , Surveys and Questionnaires , Young Adult
19.
Psychopharmacology (Berl) ; 224(1): 121-32, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22903359

ABSTRACT

RATIONALE: Social environment influences alcohol consumption in humans; however, animal models have only begun to address biological underpinnings of these effects. OBJECTIVES: We investigated whether social influences on alcohol drinking in the prairie vole are specific to the sex of the social partner. METHODS: In Experiment 1, control, sham, and gonadectomized voles were placed either in mesh-divided housing with a same-sex sibling or isolation with access to ethanol. In Experiment 2, animals were given an elevated plus maze test (EPM) and then females were paired with a castrated male followed by isolation or mesh-divided housing with access to ethanol. In Experiment 3, subjects categorized as low or high drinkers based on initial ethanol intake were placed in mesh-divided housing with an opposite-sex partner of the same or opposite drinking group and ethanol access. Subjects were then moved back to isolation for a final ethanol access period. RESULTS: Same-sex pairs showed social facilitation of drinking similar to previous reports. Gonadectomy did not affect alcohol drinking. Opposite-sex paired animals in Experiment 2 did not differ in alcohol drinking based on social housing. EPM measures suggested a relationship between anxiety-like behaviors and drinking that depended on social environment. Experiment 3 identified moderate changes in alcohol preference based on social housing, but these effects were influenced by the animal's own drinking behavior and were independent of their partner's drinking. CONCLUSIONS: Social influences on alcohol self-administration in prairie voles differ based on the sex of a social partner, consistent with human drinking behavior.


Subject(s)
Alcohol Drinking/psychology , Behavior, Animal , Housing, Animal , Social Environment , Animals , Arvicolinae , Castration , Ethanol/administration & dosage , Female , Humans , Male , Maze Learning , Models, Animal , Pair Bond , Sex Factors , Social Facilitation , Social Isolation , Species Specificity
20.
J Dairy Sci ; 95(10): 5985-95, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22901468

ABSTRACT

The objective of this study was to determine the efficacy of Prevotella bryantii 25A as a probiotic during a subacute ruminal acidosis (SARA) challenge using a commercial probiotic as a positive control. Six multiparous ruminally fistulated cows (BW=685 ± 65 kg; (mean ± SD) in the mid-phase of lactation (70 to 148 DIM) received the following treatments in a replicated 3×3 Latin square design: (1) total mixed ration (TMR; control, CON), (2) TMR + 2g/head per day of a probiotic combination of Enterococcus faecium and Saccharomyces cerevisiae (EFSC), or (3) TMR + Prevotella bryantii 25A. The Latin square consisted of 3 wk of adaptation to the respective treatments during which the animals were fed ad libitum once per day a conventional early-lactation TMR and 1.5 kg of hay. The adaptation was followed by 4 d of SARA (no hay) and 10d of rest (adaptation diet without probiotics). Dry matter intake and milk production were depressed during SARA (22.0 and 31.8 kg/d, respectively) compared with adaptation (24.4 and 34.0 kg/d, respectively) and did not recover during rest (22.3 and 30.7 kg/d, respectively). During SARA, P. bryantii 25A had no effect on rumen pH, whereas EFSC reduced the percentage of time with pH <6.0 (71%) compared with CON (85%) and increased maximum pH. The EFSC treatment tended to increase mean pH over 24h (5.65) compared with CON (5.45). Proportion of time with pH <5.6 tended to be lower with EFSC (46%) than with CON (62%). Populations of bacteria considered to be the most important cellulose digesters in the rumen (Ruminococcus flavefaciens, Ruminococcus albus, and Fibrobacter succinogenes) were also monitored during these treatments using culture-independent real-time PCR methods. The population of R. flavefaciens was similar between the 2 feeding phases, whereas F. succinogenes and R. albus were lower during SARA compared with rest. In light of the present study, P. bryantii 25A did not prove to be an effective preventative for SARA. The role of EFSC in regulating rumen pH was confirmed, with a possible effect of maintaining R. flavefaciens populations during SARA.


Subject(s)
Acidosis/veterinary , Cattle Diseases/metabolism , Lactation/physiology , Prevotella/metabolism , Probiotics/pharmacology , Acidosis/metabolism , Acidosis/physiopathology , Ammonia/analysis , Animal Nutritional Physiological Phenomena/physiology , Animals , Cattle , Cattle Diseases/physiopathology , Fatty Acids, Volatile/analysis , Female , Gastrointestinal Contents/chemistry , Hydrogen-Ion Concentration , Lactates/analysis , Lactation/metabolism , Milk/chemistry , Rumen/chemistry , Rumen/metabolism , Rumen/physiopathology
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