scholarly journals Two Hits of EDCs Three Generations Apart: Effects on Social Behaviors in Rats, and Analysis by Machine Learning

Toxics ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 30
Author(s):  
Ross Gillette ◽  
Michelle Dias ◽  
Michael P. Reilly ◽  
Lindsay M. Thompson ◽  
Norma J. Castillo ◽  
...  
Keyword(s):  
Machine Learning ◽  
Social Preference ◽  
Endocrine Disrupting Chemicals ◽  
Social Behaviors ◽  
Female Rats ◽  
Pregnant Rat ◽  
Three Generations ◽  
Male And Female Rats ◽  
Key Factor ◽  
Aroclor 1221

All individuals are directly exposed to extant environmental endocrine-disrupting chemicals (EDCs), and indirectly exposed through transgenerational inheritance from our ancestors. Although direct and ancestral exposures can each lead to deficits in behaviors, their interactions are not known. Here we focused on social behaviors based on evidence of their vulnerability to direct or ancestral exposures, together with their importance in reproduction and survival of a species. Using a novel “two hits, three generations apart” experimental rat model, we investigated interactions of two classes of EDCs across six generations. PCBs (a weakly estrogenic mixture Aroclor 1221, 1 mg/kg), Vinclozolin (antiandrogenic, 1 mg/kg) or vehicle (6% DMSO in sesame oil) were administered to pregnant rat dams (F0) to directly expose the F1 generation, with subsequent breeding through paternal or maternal lines. A second EDC hit was given to F3 dams, thereby exposing the F4 generation, with breeding through the F6 generation. Approximately 1200 male and female rats from F1, F3, F4 and F6 generations were run through tests of sociability and social novelty as indices of social preference. We leveraged machine learning using DeepLabCut to analyze nuanced social behaviors such as nose touching with accuracy similar to a human scorer. Surprisingly, social behaviors were affected in ancestrally exposed but not directly exposed individuals, particularly females from a paternally exposed breeding lineage. Effects varied by EDC: Vinclozolin affected aspects of behavior in the F3 generation while PCBs affected both the F3 and F6 generations. Taken together, our data suggest that specific aspects of behavior are particularly vulnerable to heritable ancestral exposure of EDC contamination, that there are sex differences, and that lineage is a key factor in transgenerational outcomes.

scholarly journals Prenatal EDCs Impair Mate and Odor Preference and Activation of the VMN in Male and Female Rats

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Morgan E Hernandez Scudder ◽  
Amy Weinberg ◽  
Lindsay Thompson ◽  
David Crews ◽  
Andrea C Gore
Keyword(s):  
Preference Test ◽  
Brain Regions ◽  
Female Rats ◽  
Early Gene ◽  
Odor Preference ◽  
Pregnant Rat ◽  
Discrimination Ability ◽  
Preference Behavior ◽  
Male And Female Rats ◽  
Aroclor 1221

Abstract Environmental endocrine-disrupting chemicals (EDCs) disrupt hormone-dependent biological processes. We examined how prenatal exposure to EDCs act in a sex-specific manner to disrupt social and olfactory behaviors in adulthood and underlying neurobiological mechanisms. Pregnant rat dams were injected daily from embryonic day 8 to 18 with 1 mg/kg Aroclor 1221 (A1221), 1 mg/kg vinclozolin, or the vehicle (6% DMSO in sesame oil). A1221 is a mixture of polychlorinated biphenyls (weakly estrogenic) while vinclozolin is a fungicide (anti-androgenic). Adult male offspring exposed to A1221 or vinclozolin, and females exposed to A1221, had impaired mate preference behavior when given a choice between 2 opposite-sex rats that differed by hormone status. A similar pattern of impairment was observed in an odor preference test for urine-soaked filter paper from the same rat groups. A habituation/dishabituation test revealed that all rats had normal odor discrimination ability. Because of the importance of the ventrolateral portion of the ventromedial nucleus (VMNvl) in mate choice, expression of the immediate early gene product Fos was measured, along with its co-expression in estrogen receptor alpha (ERα) cells. A1221 females with impaired mate and odor preference behavior also had increased neuronal activation in the VMNvl, although not specific to ERα-expressing neurons. Interestingly, males exposed to EDCs had normal Fos expression in this region, suggesting that other neurons and/or brain regions mediate these effects. The high conservation of hormonal, olfactory, and behavioral traits necessary for reproductive success means that EDC contamination and its ability to alter these traits has widespread effects on wildlife and humans.

scholarly journals Social interaction with an alcohol-intoxicated or cocaine-injected peer selectively alters social behaviors and drinking in adolescent male and female rats

2019 ◽  
Author(s):  
Danielle M. Gamble ◽  
Chloe C. Josefson ◽  
Mary K. Hennessey ◽  
Ashley M. Davis ◽  
Renee C. Waters ◽  
...  
Keyword(s):  
Social Interaction ◽  
Alcohol Drinking ◽  
Social Play ◽  
Social Behaviors ◽  
Ethanol Intake ◽  
Female Rats ◽  
Adolescent Male ◽  
Saccharin Consumption ◽  
Male And Female ◽  
Male And Female Rats

AbstractBackgroundDrinking alcohol is facilitated by social interactions with peers, especially during adolescence. The importance of peer social influences during adolescence on alcohol and substance use have recently received more attention. We have shown that social interaction with an alcohol-intoxicated peer influences adolescent alcohol drinking differently in male and female rats using the demonstrator-observer paradigm. The present set of experiments analyzed the social interaction session to determine behaviors that influence alcohol drinking in adolescent male and female rats.MethodsSpecifically, in experiment one we determined which behaviors were altered during social interaction with an alcohol-intoxicated demonstrator and assessed changes in ethanol intake in adolescent observers. Experiment two examined changes in voluntary saccharin consumption to determine if social interaction with an alcohol-intoxicated demonstrator altered consumption of a palatable solution. In experiment three, we administered a low (5 mg/kg) or high (20 mg/kg) dose of cocaine to the demonstrator and assessed changes in the adolescent observers to determine if social interaction with a ‘drugged’ peer altered social behaviors and voluntary ethanol intake.ResultsWe showed that social interaction with an alcohol-intoxicated demonstrator (1) decreased social play and increased social investigation and social contact in adolescent male and female observers, (2) did not alter non-social behaviors, (3) did not alter saccharin consumption and (4) increased voluntary ethanol intake in adolescent female but not male observers. When the peer was injected with cocaine (1) social play was dose-dependently decreased, (2) there were no changes in other social or non-social behaviors, and (3) voluntary ethanol intake in adolescent male and female observers was unaffected.ConclusionsThe present results are consistent and extend our previous work showing that social interaction with an alcohol-intoxicated peer selectively alters social behaviors and alcohol-drinking in adolescent rats. Females appear to be more sensitive to elevating effects of social interaction on voluntary ethanol consumption.

scholarly journals Effects of post-weaning social isolation on social behaviors and oxytocinergic activity in male and female rats

Heliyon ◽  
2019 ◽  
Vol 5 (5) ◽  
pp. e01646 ◽  
Author(s):  
Kenjiro Tanaka ◽  
Yoji Osako ◽  
Kou Takahashi ◽  
Chiharu Hidaka ◽  
Koichi Tomita ◽  
...  
Keyword(s):  
Social Isolation ◽  
Social Behaviors ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats

2018 ◽  
Author(s):  
Elena I. Varlinskaya ◽  
Linda Patia Spear ◽  
Marvin R. Diaz
Keyword(s):  
Social Behavior ◽  
Social Preference ◽  
Social Consequences ◽  
Female Rats ◽  
Prior History ◽  
Social Avoidance ◽  
Sprague Dawley ◽  
Social Investigation ◽  
Play Fighting ◽  
Male And Female Rats

AbstractThe dynorphin/kappa (DYN/KOR) system has been identified as a primary target of stress due to behavioral effects, such as dysphoria, aversion, and anxiety-like alterations that result from activation of this system. Numerous adaptations in the DYN/KOR system have also been identified in response to stress. However, whereas most studies examining the function of the DYN/KOR system have been conducted in adults, there is growing evidence suggesting that this system is ontogenetically regulated. Likewise, the outcome of exposure to stress also differs across ontogeny. Based on these developmental similarities, the objective of this study was to systematically test effects of a selective KOR agonist, U62066, on various aspects of social behavior across ontogeny in non-stressed male and female rats as well as in males and females with a prior history of repeated exposure to restraint (90 min/day, 5 exposures). We found that the social consequences of repeated restraint differed as a function of age: juvenile stress produced substantial increases in play fighting, whereas adolescent and adult stress resulted in decreases in social investigation and social preference. The KOR agonist U62066 dose-dependently reduced social behaviors in non-stressed adults, producing social avoidance at the highest dose tested, while younger animals displayed reduced sensitivity to this socially suppressing effect of U62066. Interestingly, in stressed animals, the socially suppressing effects of the KOR agonist were blunted at all ages, with juveniles and adolescents exhibiting increased social preference in response to certain doses of U62066. Taken together, these findings support the hypothesis that the DYN/KOR system changes with age and differentially responds and adapts to stress across development.

scholarly journals Social Interaction With an Alcohol‐Intoxicated or Cocaine‐Injected Peer Selectively Alters Social Behaviors and Drinking in Adolescent Male and Female Rats

2019 ◽  
Vol 43 (12) ◽  
pp. 2525-2535 ◽  
Author(s):  
Danielle N. Gamble ◽  
Chloe C. Josefson ◽  
Mary K. Hennessey ◽  
Ashley M. Davis ◽  
Renee C. Waters ◽  
...  
Keyword(s):  
Social Interaction ◽  
Social Behaviors ◽  
Female Rats ◽  
Adolescent Male ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Comparative Assessment of Familiarity/Novelty Preferences in Rodents

2021 ◽  
Vol 15 ◽  
Author(s):  
Annaliese K. Beery ◽  
Katharine L. Shambaugh
Keyword(s):  
Social Behavior ◽  
Social Preference ◽  
Social Groups ◽  
Female Rats ◽  
Data Sets ◽  
Prairie Voles ◽  
Meadow Voles ◽  
Male And Female Rats ◽  
High Degree

Sociality—i.e., life in social groups—has evolved many times in rodents, and there is considerable variation in the nature of these groups. While many species-typical behaviors have been described in field settings, the use of consistent behavioral assays in the laboratory provides key data for comparisons across species. The preference for interaction with familiar or novel individuals is an important dimension of social behavior. Familiarity preference, in particular, may be associated with more closed, less flexible social groups. The dimension from selectivity to gregariousness has been used as a factor in classification of social group types. Laboratory tests of social choice range from brief (10 minutes) to extended (e.g., 3 hours). As familiarity preferences typically need long testing intervals to manifest, we used 3-hour peer partner preference tests to test for the presence of familiarity preferences in same-sex cage-mates and strangers in rats. We then conducted an aggregated analysis of familiarity preferences across multiple rodent species (adult male and female rats, mice, prairie voles, meadow voles, and female degus) tested with the same protocol. We found a high degree of consistency within species across data sets, supporting the existence of strong, species-typical familiarity preferences in prairie voles and meadow voles, and a lack of familiarity preferences in other species tested. Sociability, or total time spent near conspecifics, was unrelated to selectivity in social preference. These findings provide important background for interpreting the neurobiological mechanisms involved in social behavior in these species.

Monosodium glutamate administration early in life alters pineal melatonin nocturnal profile in adulthood

2021 ◽  
Vol 4 (1) ◽  
pp. 99-114
Author(s):  
Janaína B Garcia ◽  
Fernanda G Do Amaral ◽  
Daniela C Buonfiglio ◽  
Rafaela FA Vendrame ◽  
Patrícia L Alves ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Pineal Gland ◽  
Serum Insulin ◽  
Monosodium Glutamate ◽  
Female Rats ◽  
Pineal Melatonin ◽  
Melatonin Synthesis ◽  
Male And Female Rats ◽  
Melatonin Production

The pineal gland synthesizes melatonin exclusively at night, which gives melatonin the characteristic of a temporal synchronizer of the physiological systems. Melatonin is a regulator of insulin activities centrally and also peripherally and its synthesis is reduced in diabetes.  Since monosodium glutamate (MSG) is often used to induce the type 2 diabetic and metabolic syndrome in animal models, the purpose of this work is to evaluate the potential effects of MSG given to neonates on the pineal melatonin synthesis in different aged male and female rats. Wistar rats were subcutaneously injected with MSG (4mg/g/day) or saline solution (0.9%) from the second to eighth post-natal day. The circadian profiles both melatonin levels and AANAT activity were monitored at different ages. Body weight, naso-anal length, adipose tissues weight, GTT, ITT and serum insulin levels were also evaluated. Typical obesity with the neonatal MSG treatment was observed, indicated by a great increase in adipose depots without a concurrent increase in body weight. MSG treatment did not cause hyperglycemia or glucose intolerance, but induced insulin resistance. An increase of melatonin synthesis at ZT 15 with phase advance was observed in in some animals. The AANAT activity was positively parallel to the melatonin circadian profile. It seems that MSG causes hypothalamic obesity which may increase AANAT activity and melatonin production in pineal gland. These effects were not temporally correlated with insulin resistance and hyperinsulinemia indicating the hypothalamic lesions, particularly in arcuate nucleus induced by MSG in early age, as the principal cause of the increase in melatonin production.

THE PITUITARY AND ADRENAL RESPONSES TO ADMINISTRATION OF OESTRIOL IN GONADECTOMIZED RATS

1961 ◽  
Vol 38 (1) ◽  
pp. 50-58 ◽  
Author(s):  
N. E. Borglin ◽  
L. Bjersing
Keyword(s):  
Pituitary Gland ◽  
Adrenal Cortex ◽  
Clinical Experience ◽  
Uterine Cervix ◽  
Morphological Changes ◽  
Physiological Significance ◽  
Female Rats ◽  
Experimental Conditions ◽  
Male And Female ◽  
Male And Female Rats

ABSTRACT Oestriol (oestra-1,3,5(10)-triene-3,16α,17β-triol) is a weakly oestrogenic substance which, however, in contrast to what was formerly believed, is of physiological significance. Its effect is localized largely to the uterine cervix and vagina. Clinical experience argues both for and against an effect on the pituitary gland. This investigation is concerned with the morphological changes in the pituitary gland and adrenal cortex of gonadectomized male and female rats after the injection of oestriol. It was found that oestriol has the same type of action on these glands as other oestrogens, but under the experimental conditions used, this effect proved much weaker than that produced by oestradiol (oestra-1,3,5(10)-triene-3,17β-diol).

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