scholarly journals 5-HT3 receptor signaling in serotonin transporter-knockout rats: a female sex-specific animal model of visceral hypersensitivity

2019 ◽  
Vol 316 (1) ◽  
pp. G132-G143 ◽  
Author(s):  
Nadine El-Ayache ◽  
James J. Galligan
Keyword(s):  
Serotonin Transporter ◽  
Visceral Pain ◽  
Gene Knockout ◽  
Visceral Hypersensitivity ◽  
Female Rats ◽  
Male Rats ◽  
Receptor Signaling ◽  
Receptor Antagonists ◽  
Female Sex ◽  
Balloon Distention

The irritable bowel syndrome (IBS) is a functional gastrointestinal motor and visceral sensation disorder that is more common in women than men. Female serotonin transporter (SERT)-gene knockout (KO) rats exhibit hypersensitivity to colorectal balloon distention (CRD) that mimics colonic hypersensitivity occurring in female IBS patients. Alosetron (5-HT3 receptor antagonist) is used to treat diarrhea-predominant IBS in female patients. Other 5-HT3 receptor antagonists are ineffective at treating IBS symptoms. The visceromotor response (VMR) to CRD in SERT-KO and wild-type (WT) rats was measured following subcutaneous (sc), intracerobroventricular (icv), or intrathecal (it) treatment with 5-HT3 receptor antagonists and an agonist. Alosetron (sc) and granisetron (antagonists) caused a paradoxical increase in the VMR to CRD in SERT-KO female rats. Alosetron (sc) increased the VMR to CRD in WT male rats. Alosetron (it) increased the VMR to CRD in SERT-KO female rats only, and the 5-HT3 receptor agonist SR-52772 increased the VMR to CRD in SERT-KO male rats. Depletion of spinal 5-HT using 5,7-dihydroxytryptamine prevented the increase in VMR to CRD in SERT-KO female and male rats treated it with alosetron and SR-52772, respectively. Alosetron (icv) did not affect the VMR to CRD in WT or KO female rats, but it increased the VMR in male SERT-KO but not WT male rats. These data suggest that 5-HT3 receptor signaling at the dorsal spinal cord mediates visceral hypersensitivity in female SERT-KO rats. Such differences could facilitate development of sex-specific drug treatments for visceral pain. NEW & NOTEWORTHY We studied a model of female sex-specific visceral hypersensitivity using rats that had a loss of function of the serotonin transporter (SERT) caused by gene truncation. Female SERT-KO rats exhibited visceral hypersensitivity in response to colorectal balloon distention. We found that increased 5-HT signaling at dorsal spine 5-HT3 receptors was responsible for visceral hypersensitivity in female but not male SERT-KO rats.

scholarly journals Estrogen re-enhanced prenatal stress-related visceral sensitization and pain regulation

2020 ◽  
Author(s):  
Jinghong Chen ◽  
Ying Sun ◽  
Jinbao Wei ◽  
Peijun Ju ◽  
Qinjie Li ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Prenatal Stress ◽  
Pain Sensitivity ◽  
Visceral Pain ◽  
Afferent Fiber ◽  
Visceral Hypersensitivity ◽  
Female Rats ◽  
Primary Afferent

Abstract Background: Visceral pain is one of the most common sign of irritable bowel syndrome (IBS). Chronic stress during pregnancy may increase visceral pain sensitivity of offspring in a sexdependent way. Combining adult stress in offspring will increase this sensitivity. Based on the evidence implicating estrogen exacerbates visceral hypersensitivity in female rodents in pre-clinical models, we predicted that chronic prenatal stress (CPS) plus chronic adult stress (CAS) will maximize visceral pain sensitivity; and estrogen plays an important role in this hyperalgesia.Methods: The CPS plus CAS rodent model was established in which the balloon was used to distend colorectum. Meanwhile, the single fiber recording in vivo and patch-clamp experiments in vitro were used to monitor neuronal activity. The RT-PCR, Western Blot, and Immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent sensitivity and molecular or transmission changes. We use Ovariectomy and Letrozole to treate female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent sensitization. Letrozole mainly used to reduce estrogen levels.Results: As predicted, CPS significantly increased single unit afferent fiber activity in L6-S2 dorsal roots in response. Activity was further enhanced by CAS. And the activity in offspring females was significantly greater than the males. Besides, the excitability of colon-projecting dorsal root ganglion (DRG) neurons increases in CPS + CAS rats that was associated with a decrease in transient A-type K+ current. Letrozole treatment decreases the colon DRG neuron excitability in females by decreasing the estrogen levels. Conclusions: This study adds to the growing evidence for the development of chronic stress induced visceral hypersensitivity in female, which involves estrogen-dependent sensitization of primary afferent colon neurons. Understanding this neurophysiological mechanisms will spur the development of female pain specific therapies.

Sex differences in morphine-induced analgesia of visceral pain are supraspinally and peripherally mediated

2006 ◽  
Vol 291 (2) ◽  
pp. R307-R314 ◽  
Author(s):  
Yaping Ji ◽  
Anne Z. Murphy ◽  
Richard J. Traub
Keyword(s):  
Sex Difference ◽  
Visceral Pain ◽  
Somatic Tissue ◽  
Female Rats ◽  
Male Rats ◽  
Opioid Analgesia ◽  
Morphine Analgesia ◽  
Intact Male ◽  
Morphine Dose ◽  
Male And Female Rats

Increasing evidence suggests there is a sex difference in opioid analgesia of pain arising from somatic tissue. However, the existence of a sex difference in visceral pain and opioid analgesia is unclear. This was examined in the colorectal distention (CRD) model of visceral pain in the current study. The visceromotor response (vmr) to noxious CRD was recorded in gonadally intact male and female rats. Subcutaneous injection of morphine dose-dependently decreased the vmr in both groups without affecting colonic compliance. However, morphine was significantly more potent in male rats than females. Because systemic morphine can act at peripheral tissue and in the central nervous system (CNS), the source of the sex difference in morphine analgesia was determined. The peripherally restricted μ-opioid receptor (MOR) antagonist naloxone methiodide dose-dependently attenuated the effects of systemic morphine. Systemic administration of the peripherally restricted MOR agonist loperamide confirmed peripherally mediated morphine analgesia and revealed greater potency in males compared with females. Spinal administration of morphine dose-dependently attenuated the vmr, but there was no sex difference. Intracerebroventricular administration of morphine also dose-dependently attenuated the vmr with significantly greater potency in male rats. The present study documents a sex difference in morphine analgesia of visceral pain that is both peripherally and supraspinally mediated.

An Enriched Environment Reduces Chronic Stress-Induced Visceral Pain Through Modulating Microglial Activity in the Central Nucleus of the Amygdala

2021 ◽  
Author(s):  
Tian Yuan ◽  
Albert Orock ◽  
Beverley Greenwood-Van Meerveld
Keyword(s):  
Chronic Stress ◽  
Environmental Enrichment ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Female Rats ◽  
Central Nucleus ◽  
Dorsal Margin ◽  
Protective Effects ◽  
Male And Female Rats ◽  
Synaptic Pruning

Cognitive behavioral therapy (CBT) improves the quality of life for patients with brain-gut disorders, however, the underlying mechanisms of CBT remain to be explored. Previously we showed that environmental enrichment (EE), an experimental paradigm that mirrors positive behavioral intervention, ameliorates chronic stress-induced visceral hypersensitivity in a rodent model via mechanisms involving altered activity in the central nucleus of amygdala (CeA). In the present study, we investigated whether microglia-mediated synaptic plasticity in the CeA is a potential mechanism underlying the protective effects of EE against stress-induced visceral hypersensitivity. We sterotaxically implanted corticosterone (CORT) micropellets onto the dorsal margin of the CeA shown previously to induce colonic hypersensitivity. Animals were housed in EE cages or standard cages for 14 days following CORT implantation. Visceral sensitivity was assessed via visceromotor behavioral response to colorectal distension. Microglial morphology, microglia-mediated synaptic engulfment and the expression of synaptic pruning-related signals C1q, C3 and C3R were measured using immunofluorescence and RNAscope assay. We found that housing CORT implanted rats in EE cages for 14 days attenuated visceral hypersensitivity in both male and female rats as compared to control rats maintained in standard housing. EE reduced CORT-induced microglial remodeling and microglia-mediated synaptic pruning with reduced C1q and CR3, but not C3, expression. Our data suggest that exposure to EE is sufficient to ameliorate stress-induced visceral pain via reducing amygdala microglia-modulated neuronal plasticity.

INDUCTION OF GOITRE BY PTU OR KClO4 IN MALE AND FEMALE RATS. EFFECT OF GONADECTOMY

1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia
Keyword(s):  
Iodine Content ◽  
High Plasma ◽  
Disc Electrophoresis ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Male And Female ◽  
Glucose Levels ◽  
Male And Female Rats ◽  
Tsh Levels

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.

OXYDATION DES ANABOLIKUMS 1-METHYL-ANDROST-1-EN-17β-OL-3-ON MIT WASSERSTOFFTRANSFER AUF ÖSTRON

1971 ◽  
Vol 67 (3) ◽  
pp. 517-530 ◽  
Author(s):  
Martin Wenzel
Keyword(s):  
Rat Liver ◽  
Anabolic Steroid ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Liver Slices ◽  
Androgen Effects ◽  
Biochemical Difference

ABSTRACT With the aid of metenolon-17α-T a tritium-transfer to oestrone in rat liver slices was demonstrated. This tritium-transfer from metenolon17α-T to oestrone yielding tritium-labelled oestradiol had a higher efficiency in male than in female rat liver. Correspondingly in the presence of metenolon the relation of oestrone to oestradiol is changed more in male than in female rat liver. Looking for biochemical differences between the anabolic steroid metenolon and testosterone the oxydation at C17 was measured in different organs of the rat using 17α-T-labelled steroids. The highest oxydation rate was found for both steroids in the liver. In the sexual organs of male rats the oxydation rate of testosterone was 50–10 times higher than that of the anabolic steroid. This difference was less in sexual organs of female rats. This result of a greater biochemical difference between both steroids in males than in females leads to the question, whether the dissociation between the anabolic and the androgen effects is higher in males than in females.

The effect of dexamethasone on mucosal immunity of uterine tissue during pregnancy in rat

2019 ◽  
Vol 20 (1) ◽  
pp. 75-84
Keyword(s):  
Early Pregnancy ◽  
Histopathological Examination ◽  
Early Period ◽  
Interleukin 10 ◽  
Treated Group ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Uterine Tissue ◽  
Leukocytic Infiltration

Disturbances in early pregnancy immunity affect embryo development, endometrial receptivity, placental development, fetal growth and lead to subfertility, dexamethasone is a synthetic glucocorticoid used for treatment of various complications. Immune cells and cytokines were examined during the early pregnancy in twenty-four female rats and six male rats for mating. Rats were grouped into two group control and dexamethasone treated by a dose of 50µgm/kgm body weight daily starting from one week before mating and persisted for one week after pregnancy. Blood samples were collected from each rat at 5hrs and at 1,3,7 day of pregnancy. Extracted RNA was subjected to real time PCR to determine mRNA levels for immune related genes interleukin1a(IL1A) and interleukin 10(IL10). Histopathological examination was done to uterus in order to detect leukocyte infiltration in uterine tissue. Results showed that significant increase in white blood cell count mainly eosinophil at 5hrs and lymphocyte at three and seven day of pregnancy of dexamethasone treated group. Moreover, TNF, C-reactive protein and progesterone were increased mainly at seven day of pregnancy of dexamethasone treated group. Similarly, interleukin 1alpha and interleukin 10 significantly increased at 5hrs and one day of pregnancy of dexamethasone treated group. In contrast, serum levels of total antioxidant capacity and estrogen were decreased significantly at 5hrs and seven day in dexamethasone treated group. Histopathological examination of uterus revealed leukocytic infiltration especially neutrophil and few eosinophils at five hours and one day of gestation then eosinophil become absent at 3day and seven day of dexamethasone group. Epithelial height and uterine gland diameter significantly increased at 5hrs, three day and seven days of gestation of dexamethasone treated group. The present investigation demonstrated that using of dexamethasone by dose of 50µgm/kgm during early pregnancy had a conflicting impact on some immune cytokines and parameters and may reflect a harmful response of immune system toward early period of pregnancy

Female rats display higher methamphetamine-primed reinstatement and c-Fos immunoreactivity than male rats

2021 ◽  
pp. 173089
Author(s):  
Steven T. Pittenger ◽  
Shinnyi Chou ◽  
Nathen J. Murawski ◽  
Scott T. Barrett ◽  
Olivia Loh ◽  
...  
Keyword(s):  
Female Rats ◽  
Male Rats
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