scholarly journals Oxytocin has sex-specific effects on social behaviour and hypothalamic oxytocin immunoreactive cells but not hippocampal neurogenesis in adult rats

2019 ◽  
Author(s):  
Paula Duarte-Guterman ◽  
Stephanie E. Lieblich ◽  
Wansu Qiu ◽  
Jared E.J. Splinter ◽  
Kimberly A. Go ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Body Mass ◽  
Hippocampal Neurogenesis ◽  
Female Rats ◽  
Brain Barrier ◽  
Social Investigation ◽  
Male And Female ◽  
Specific Effects ◽  
Male And Female Rats ◽  
17Β Estradiol

AbstractOxytocin regulates social behaviours, pair bonding and hippocampal neurogenesis but most studies have used adult males. Our study investigated the effects of oxytocin on social investigation and adult hippocampal neurogenesis in male and female rats. Oxytocin has poor penetration of the blood-brain barrier, therefore we tested a nanoparticle drug, TRIOZANTM (Ovensa Inc.), which permits greater blood-brain-barrier penetration. Adult male and female rats were injected daily (i.p.) for 10 days with either: oxytocin in PBS (0.5 or 1.0 mg/kg), oxytocin in TRIOZANTM (0.5 or 1.0 mg/kg), or vehicle (PBS) and tested for social investigation. Oxytocin decreased body mass and increased social investigation and number of oxytocin-immunoreactive cells in the supraoptic nucleus (SON) of the hypothalamus in male rats only. In both sexes, oxytocin decreased the number of immature neurons (doublecortin+ cells) in the ventral hippocampus and reduced plasma 17β-estradiol levels in a dose- and delivery-dependent way. Oxytocin in TRIOZANTM reduced sedation observed post-injection and increased some central effects (oxytocin levels in the hypothalamus and ventral hippocampus neurogenesis) relative to oxytocin in PBS indicating that the nanoparticle may be used as an alternative brain delivery system. We showed that oxytocin has sex-specific effects on social investigation, body mass, sedation, and the oxytocin system. In contrast, similar effects were observed in both sexes in neurogenesis and plasma 17β-estradiol. Our work suggests that sex differences in oxytocin regulation of brain endpoints is region-specific (hypothalamus versus hippocampus) and that oxytocin does not promote social investigation in females.

scholarly journals 2,4,6-Tribromophenol Exposure Decreases P-Glycoprotein Transport at the Blood-Brain Barrier

2019 ◽  
Vol 171 (2) ◽  
pp. 463-472 ◽  
Author(s):  
Andrew W Trexler ◽  
Gabriel A Knudsen ◽  
Sascha C T Nicklisch ◽  
Linda S Birnbaum ◽  
Ronald E Cannon
Keyword(s):  
Blood Brain Barrier ◽  
Ex Vivo ◽  
Female Rats ◽  
Brain Barrier ◽  
Transport Activity ◽  
Fish Food ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Male And Female Rats

Abstract 2,4,6-Tribromophenol (TBP, CAS No. 118-79-6) is a brominated chemical used in the production of flame-retardant epoxy resins and as a wood preservative. In marine environments, TBP is incorporated into shellfish and consumed by predatory fish. Food processing and water treatment facilities produce TBP as a byproduct. 2,4,6-Tribromophenol has been detected in human blood and breast milk. Biologically, TBP interferes with estrogen and thyroid hormone signaling, which regulate important transporters of the blood-brain barrier (BBB). The BBB is a selectively permeable barrier characterized by brain microvessels which are composed of endothelial cells mortared by tight-junction proteins. ATP-binding cassette (ABC) efflux transporters on the luminal membrane facilitate the removal of unwanted endobiotics and xenobiotics from the brain. In this study, we examined the in vivo and ex vivo effects of TBP on two important transporters of the BBB: P-glycoprotein (P-gp, ABCB1) and Multidrug Resistance-associated Protein 2 (MRP2, ABCC2), using male and female rats and mice. 2,4,6-Tribromophenol exposure ex vivo resulted in a time- (1–3 h) and dose- (1–100 nM) dependent decrease in P-gp transport activity. MRP2 transport activity was unchanged under identical conditions. Immunofluorescence and western blotting measured decreases in P-gp expression after TBP treatment. ATPase assays indicate that TBP is not a substrate and does not directly interact with P-gp. In vivo dosing with TBP (0.4 µmol/kg) produced decreases in P-gp transport. Co-treatment with selective protein kinase C (PKC) inhibitors prevented the TBP-mediated decreases in P-gp transport activity.

Dextromethorphan affects ventilation differently in male and female rats

1996 ◽  
Vol 81 (5) ◽  
pp. 1911-1916 ◽  
Author(s):  
Evelyn H. Schlenker
Keyword(s):  
Oxygen Consumption ◽  
Aspartic Acid ◽  
Subcutaneous Administration ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Time Points ◽  
Specific Effects ◽  
Male And Female Rats ◽  
Gender Specific

Schlenker, Evelyn H. Dextromethorphan affects ventilation differently in male and female rats. J. Appl. Physiol. 81(5): 1911–1916, 1996.—Subcutaneous administration of aspartic acid results in a long-lasting but reversible depression of ventilation in male but not in female rats. Aspartic acid acts on N-methyl-d-aspartate receptors. The present study tested the hypothesis that a noncompetitive N-methyl-d-aspartate-receptor antagonist, dextromethorphan (Dex), would depress ventilation in female rats and stimulate it in male rats. Moreover, Dex administered prior to aspartic acid should prevent the aspartic acid-induced depression of ventilation in male rats. In female rats, Dex caused a 30% depression of ventilation relative to saline at 5 and 10 mg/kg ( P < 0.01) but not at the highest dose (20 mg/kg). In male rats, Dex had no effect on ventilation. At a dose of 20 mg/kg, Dex depressed oxygen consumption to 50% of the saline value at all time points in female rats ( P < 0.001) and in male rats 45 and 60 min after administration. The time points when Dex depressed ventilation and oxygen consumption were different in female rats, suggesting that the depression of ventilation was not the result of a depression in oxygen consumption. During a hypercapnic challenge (7% CO2), female rats treated with 5 and 10 mg/kg of Dex exhibited a smaller increase in ventilatory response relative to saline treatment. At a dose of 20 mg/kg, the hypercapnic responsiveness of male rats was markedly stimulated (85.8 ± 8.95 ml/min) relative to saline (50.6 ± 9.14 ml/min; P < 0.001). Finally, Dex administered before aspartic acid prevented the aspartic acid-induced depression of ventilation in male rats. Thus, in rats, Dex has gender-specific effects on ventilation and these effects are not associated with changes in oxygen consumption.

scholarly journals Regionally Specific Effects of Oxytocin on Reinstatement of Cocaine Seeking in Male and Female Rats

2018 ◽  
Vol 21 (7) ◽  
pp. 677-686 ◽  
Author(s):  
Rachel A Weber ◽  
Carly N Logan ◽  
Kah-Chung Leong ◽  
Joanna Peris ◽  
Lori Knackstedt ◽  
...  
Keyword(s):  
Female Rats ◽  
Male And Female ◽  
Specific Effects ◽  
Male And Female Rats ◽  
Cocaine Seeking

scholarly journals IMPACT OF ADOLESCENT INTERMITTENT ETHANOL EXPOSURE IN MALE AND FEMALE RATS ON SOCIAL DRINKING AND NEUROPEPTIDE GENE EXPRESSION

2021 ◽  
Author(s):  
Trevor Towner ◽  
Kimberly M Papastrat ◽  
Linda P Spear ◽  
Elena I Varlinskaya ◽  
David F Werner
Keyword(s):  
Gene Expression ◽  
Social Behavior ◽  
Lateral Septum ◽  
Female Rats ◽  
Dependent Manner ◽  
Social Investigation ◽  
Male And Female ◽  
Male And Female Rats ◽  
Social Drinking ◽  
Drinking Ethanol

Background: Alcohol use during adolescence can alter maturational changes that occur in brain regions associated with social and emotional responding. Our previous studies have shown that adult male, but not female rats demonstrate social anxiety-like alterations and enhanced sensitivity to ethanol-induced social facilitation following adolescent intermittent ethanol (AIE) exposure. These consequences of AIE may influence adult social drinking in a sex-specific manner. Methods: To test effects of AIE on social drinking, male and female Sprague-Dawley rats exposed to water or ethanol [0 or 4 g/kg, intragastrically, every other day, between postnatal day (P) 25 and 45] were tested as adults (P72-83) in a social drinking paradigm (30-minute access to a 10% ethanol solution in supersac or supersac alone in groups of three same-sex littermates across two 4-day cycles separated by 4 days off). Social behavior was assessed during the last drinking session, with further assessment of oxytocin (OXT), oxytocin receptor (OXTR), vasopressin (AVP) and vasopressin receptors 1a and 1b (AVPR1a, AVPR1b) in the hypothalamus and lateral septum. Results: Males exposed to AIE consumed more ethanol than water-exposed controls during the second drinking cycle, whereas AIE did not affect supersac intake in males. AIE-exposed females consumed less ethanol and more supersac than water-exposed controls. Water-exposed females drinking ethanol showed more social investigation as well as significantly higher hypothalamic OXTR, AVP, and AVPR1b gene expression than their counterparts ingesting supersac and AIE females drinking ethanol. In males, hypothalamic AVPR1b gene expression was affected by drinking solution, with significantly higher expression evident in males drinking ethanol than those consuming supersac. Conclusions: Collectively, these findings provide new evidence regarding sex-specific effects of AIE on social drinking and suggest that the hypothalamic OXT and AVP systems are implicated in the effects of ingested ethanol on social behavior in a sex- and adolescent exposure-dependent manner.

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