Sex Differences in Cholinergic Analgesia I

Background Cholinergic agents produce analgesia after systemic and intrathecal administration. A retrospective review showed that intrathecal neostigmine was more potent in women than in men, suggesting a sex difference in this response. The purpose of this study was to determine whether such a sex difference exists in normal rats and to examine the pharmacologic mechanisms that underlie this difference. Methods Male and female rats with indwelling intrathecal catheters received injections of neostigmine, bethanechol (muscarinic agonist), or RJR-2403 (neuronal nicotinic agonist) alone or with atropine (muscarinic antagonist), mecamylamine (nicotinic antagonist), or phentolamine alpha-adrenergic antagonist) with antinociception determined to a noxious heat stimulus to the hind paw. Time versus subcutaneous paw temperature relationships were defined for males and females. Results Neostigmine produced dose-dependent antinociception with five times greater potency in female than in male rats. Neostigmine-induced antinociception was reversed in male rats by atropine and unaffected by mecamylamine, whereas it was partially reduced by each antagonist alone in females and completely reversed after injection of both. RJR-2403 was more potent in females than in males, whereas there was no sex difference to bethanechol. Phentolamine partially reversed antinociception from RJR-2403 in females. Paw temperature increased more rapidly in females than in males for the same lamp intensity. Conclusions These data demonstrate a large sex difference in antinociception to intrathecal neostigmine that is primarily the result of a nicotinic component in females. Phentolamine reversal suggests that part of this nicotinic component may rely on spinal norepinephrine release. A better understanding of this sex difference could lead to development of novel pain therapy for women.

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Sex Differences in Cholinergic Analgesia II

Anesthesiology ◽

10.1097/00000542-199911000-00039 ◽

1999 ◽

Vol 91 (5) ◽

pp. 1455-1455 ◽

Cited By ~ 29

Author(s):

Patricia M. Lavand'homme ◽

James C. Eisenach

Keyword(s):

Nerve Injury ◽

Sex Difference ◽

Female Rats ◽

Male Rats ◽

Saline Control ◽

Muscarinic Agonist ◽

Intraplantar Injection ◽

Male And Female Rats ◽

Adrenergic Antagonist ◽

Cholinergic Agents

Background Cholinergic agents reduce allodynia after nerve injury in animals and may be useful in the treatment of neuropathic pain. Intrathecally administered neostigmine and neuronal nicotinic agonists are more potent in female than in male rats against acute thermal noxious stimuli. The purpose of this study was to determine whether there is also a sex difference in the antiallodynic effects of intrathecal cholinomimetic agents in two models of allodynia and to test their pharmacologic mechanisms. Methods Male and female rats with indwelling intrathecal catheters received injections of neostigmine, bethanechol (muscarinic agonist), RJR-2403 (neuronal nicotinic agonist) alone or with atropine (muscarinic antagonist), mecamylamine (nicotinic antagonist), phentolamine (alpha-adrenergic antagonist), or saline control. The effect of these agents was determined on mechanical allodynia produced by either intraplantar injection of capsaicin or ligation of spinal nerves. Results Neostigmine and RJR-2403 but not bethanechol were more potent in female than in male rats in reducing allodynia after nerve injury, and antagonist studies were also consistent with a nicotinic component to explain this sex difference. Phentolamine did not reverse neostigmine's effect. In contrast, for capsaicin-induced allodynia, neostigmine plus mecamylamine but not neostigmine or RJR-2403 was more potent in female than in male rats. Conclusions These data demonstrate a sex difference of intrathecal neostigmine after nerve injury-induced allodynia similar to that observed in normal animals that received acute noxious thermal stimulation. However, this sex difference is not universal to all pain models because it was not present after intradermal capsaicin injection, nor is its interaction with spinal noradrenergic mechanisms consistent in all models.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00824.2005 ◽

2006 ◽

Vol 291 (2) ◽

pp. R307-R314 ◽

Cited By ~ 52

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.

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Sex difference in growth hormone feedback in the rat

Journal of Endocrinology ◽

10.1677/joe.0.1260027 ◽

1990 ◽

Vol 126 (1) ◽

pp. 27-35 ◽

Cited By ~ 35

Author(s):

L. M. S. Carlsson ◽

R. G. Clark ◽

I. C. A. F. Robinson

Keyword(s):

Growth Hormone ◽

Sex Difference ◽

Female Rats ◽

Male Rats ◽

Constant Infusion ◽

Physiological Control ◽

Sampling System ◽

Male And Female ◽

Gh Secretion ◽

Male And Female Rats

ABSTRACT Growth hormone inhibits its own secretion in animals and man but the mechanism for this inhibition is unclear: both stimulation of somatostatin release and inhibition of GH-releasing factor (GRF) release have been implicated. We have now studied the GRF responsiveness of conscious male and female rats under conditions of GH feedback induced by constant infusion of exogenous human GH (hGH). Intravenous infusions of hGH (60 μg/h) were maintained for 3 to 6 h whilst serial injections of GRF(1–29)NH2 (0·2–1 μg) were given at 45-min intervals. The GH responses were studied by assaying blood samples withdrawn at frequent intervals using an automatic blood sampling system. We have confirmed that male and female rats differ in their ability to respond to a series of GRF injections; female rats produced consistent GH responses for up to 13 consecutive GRF injections, whereas male rats showed a 3-hourly pattern of intermittent responsiveness. In female rats, multiple injections of GRF continued to elicit uniform GH responses during hGH infusions, whereas hGH infusions in male rats disturbed their intermittent pattern of responsiveness to GRF, and their regular 3-hourly cycle of refractoriness was prolonged. We suggest that this sex difference in GH feedback may be due to GH altering the pattern of endogenous somatostatin release differentially in male and female rats. Such a mechanism of GH autofeedback could be involved in the physiological control of the sexually differentiated pattern of GH secretion in the rat. Journal of Endocrinology (1990) 126, 27–35

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PUBERTAL MANIFESTATION OF SEX DIFFERENCE IN CIRCADIAN RHYTHM OF CORTICOTROPHIN-RELEASING ACTIVITY IN THE RAT HYPOTHALAMUS

Acta Endocrinologica ◽

10.1530/acta.0.0860225 ◽

1977 ◽

Vol 86 (2) ◽

pp. 225-234 ◽

Cited By ~ 13

Author(s):

Sato Honma ◽

Tsutomu Hiroshige

Keyword(s):

Circadian Rhythm ◽

Sex Difference ◽

Developmental Change ◽

Marked Change ◽

Female Rats ◽

Male Rats ◽

Ovarian Activity ◽

Essential Difference ◽

Male And Female ◽

Male And Female Rats

ABSTRACT Post-natal development of the circadian rhythm of hypothalamic content of corticotrophin-releasing factor (CRF) was examined in male and female rats, separately. CRF activity was estimated by the intrapituitary injection technique. The circadian rhythm of the CRF content observed at the third week was without any noticeable sex difference: both male and female rats began their circadian rhythm with higher values in the afternoon than in the morning. Male rats maintained this pattern up to maturity. In contrast, female rats showed a marked change at ages of fifth to sixth week: the CRF rhythm in female rats changed to a female pattern, with higher values in the morning than in the afternoon. During this period, the vaginal opening occurred concurrently with a marked afternoon rise in the plasma corticosterone, characteristic of mature female rats. On the other hand, no essential difference could be observed between male and female rats in the developmental change in the circadian rhythm of locomotor activity. These results indicate that a sex difference in the CRF rhythm is not essentially related to the process of sex differentiation in the central nervous system, but is rather related to changes in ovarian activity following the onset of puberty.

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SEX DIFFERENCES IN THE CONCENTRATIONS OF GLUCOCORTICOID RECEPTORS IN RAT LIVER AND THYMUS

Journal of Endocrinology ◽

10.1677/joe.0.0800021 ◽

1979 ◽

Vol 80 (1) ◽

pp. 21-26 ◽

Cited By ~ 13

Author(s):

D. B. ENDRES ◽

R. J. MILHOLLAND ◽

F. ROSEN

Keyword(s):

Sex Differences ◽

Sex Difference ◽

Glucocorticoid Receptors ◽

Plasma Corticosterone ◽

Female Rats ◽

Male Rats ◽

Ovariectomized Rats ◽

Intact Male ◽

Male And Female ◽

Male And Female Rats

The effects in rats of adrenalectomy, hypophysectomy, ovariectomy or combinations of these operations on the concentrations of glucocorticoid receptors in the cytosol of liver and thymus were measured. The concentrations of glucocorticoid receptors were lower in cytosols from liver and thymus of female than of male rats. After adrenalectomy, there was a significant increase in the concentrations of receptors measured in the cytoplasm from the liver and thymus of female rats and from the liver of male rats. After adrenalectomy or hypophysectomy, there was no sex difference in the concentrations of glucocorticoid receptors in cytosols of liver or thymus. After ovariectomy, the concentration of receptors in cytosols from the thymus, but not from the liver, increased. Ovariectomized rats responded to adrenalectomy in the same way as intact male rats. The different responses shown by male and female rats to endocrine manipulation probably depend upon associated changes in plasma corticosterone concentrations which are influenced by the ovary. Differences in response between the liver and thymus probably reflect a preferential distribution of corticosterone to the liver rather than to the thymus.

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Sex differences in the cardiovascular and renal actions of vasopressin in conscious rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.272.1.r370 ◽

1997 ◽

Vol 272 (1) ◽

pp. R370-R376 ◽

Cited By ~ 3

Author(s):

Y. X. Wang ◽

J. T. Crofton ◽

L. Share

Keyword(s):

Sex Difference ◽

Free Water ◽

Urine Osmolality ◽

Urine Flow ◽

Female Rats ◽

Male Rats ◽

Separate Experiment ◽

Free Water Clearance ◽

Dose Dependent ◽

Antidiuretic Action

The present study was carried out to investigate whether prostaglandins (PG) are involved in the mechanism that contributes to the sex difference in the antidiuretic and pressor actions of vasopressin. The experiments were performed in conscious male and nonestrous female rats. In hydrated rats, the graded infusion of vasopressin (10-1,000 pg.min 1.kg body wt-1) resulted in a dose-dependent antidiuresis: decreases in urine flow and free water clearance and an increase in urine osmolality. These responses were significantly greater in male than in nonestrous female rats. Pretreatment with a cyclooxygenase inhibitor, indomethacin (10 mg/kg body wt iv), significantly enhanced the antidiuretic response to vasopressin in both sexes. However, the magnitude of this enhancement was greater in female than in male rats. Thus indomethacin abolished the sex difference in the antidiuretic response to vasopressin. In a separate experiment in rats without water hydration and urine collection, infusion of pressor doses of vasopressin (1,000-6,000 pg.min-1.kg body wt-1) resulted in a greater increase in blood pressure in male than in nonestrous female rats. Treatment with indomethacin enhanced this response equivalently in both sexes and thus did not affect the sex difference in the pressor action of vasopressin. These data indicate that renal PG may mediate, at least in part, the sex difference in the antidiuretic action of vasopressin, whereas vascular PG seem not to play an important role in the sex difference in the pressor action of vasopressin.

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Roles of Up-Regulated Expression of ASIC3 in Sex Difference of Acid-Induced Duodenal HCO3 - Responses

Current Pharmaceutical Design ◽

10.2174/1381612826666200417170319 ◽

2020 ◽

Vol 26 (25) ◽

pp. 3001-3009 ◽

Cited By ~ 1

Author(s):

Koji Takeuchi ◽

Yumi Ohashi ◽

Kikuko Amagase

Keyword(s):

Sex Difference ◽

Repeated Administration ◽

Female Rats ◽

Male Rats ◽

Tamoxifen Treatment ◽

Dependent Manner ◽

Protective Mechanisms ◽

Mucosal Acidification ◽

Male And Female Rats ◽

Regulated Expression

Although the morbidity of ulcers is statistically higher in males than females, the mechanism of this difference remains unknown. Recent studies show that duodenal HCO3 - response to mucosal acidification is higher in females than males, and this may be a factor responsible for the sex difference in the mucosal protective mechanisms. In this article, we examined the duodenal HCO3 - responses to various stimuli in male and female rats, including estrogen, and reviewed the mechanisms responsible for the sex difference in the acid-induced HCO3 - secretion. Mucosal acidification was performed by exposing the duodenum to 10 mM HCl for 10 min. PGE2 was administered intravenously, while capsaicin was applied topically to the duodenum for 10 min. Tamoxifen was given s.c. 30 min before the acidification. Ovariectomy was performed 2 weeks before the experiments; half of the animals were given estrogen i.m. after the operation. Mucosal acidification increased duodenal HCO3 - secretion in male rats, and this response was inhibited by indomethacin and sensory deafferentation. Although no sex difference was found in HCO3 - responses to PGE2 and capsaicin, the response to acid was significantly greater in female than male rats. The different HCO3 - response to acid disappeared on ovariectomy, and this effect was totally reversed by the repeated administration of estrogen. The gene expression of ASIC3 in female rats was greater than in male rats and down-regulated by ovariectomy or tamoxifen treatment in an estradiol- dependent manner, while no sex difference was observed in TRPV1 and CFTR expressions. In conclusion, the acid-induced HCO3 - response is greater in female than male rats, and this phenomenon is not due to changes in PGE2 sensitivity or TRPV1/CFTR expressions but may be accounted for by increased expression of ASIC3 on sensory neurons, which is associated with the chronic influence of estrogen.

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EFFECTS OF HORMONES ON HEPATIC GLUCOSE 6-PHOSPHATE DEHYDROGENASE OF RAT

Journal of Histochemistry & Cytochemistry ◽

10.1177/15.9.530 ◽

1967 ◽

Vol 15 (9) ◽

pp. 530-534 ◽

Cited By ~ 31

Author(s):

SAMUEL H. HORI ◽

SEI-ICHI MATSUI

Keyword(s):

Enzyme Activity ◽

Sex Difference ◽

Total Activity ◽

Estradiol Benzoate ◽

Isozyme Pattern ◽

Female Rats ◽

Male Rats ◽

Total Enzyme Activity ◽

Male And Female Rats ◽

Glucose 6 Phosphate Dehydrogenase

The effects of hormones on the total activity and the isozyme pattern of glucose 6-phosphate dehydrogenase of livers of normal, castrated and adrenalectomized rats were studied. Sex difference in total enzyme activity and in the activity of one of the seven isozymes separated electrophoretically (band D enzyme) has been confirmed. Orchidectomy did not affect appreciably the enzyme activity; ovariectomy of young rats reduced the enzyme activity and abolished the sex difference. Adrenalectomy slightly reduced the enzyme activity in male and female rats, but did not eliminate the sex difference in isozyme pattern. Injection of dehydroepiandrosterone into normal and castrated female rats lowered the enzyme activity, whereas administration of estradiol benzoate to normal and castrated male rats strikingly increased the enzyme activity. In estradiol-treated males the isozyme pattern become female type. The effect of estradiol was inhibited by puromycin. Estradiol stimulated but dehydroepiandrosterone had little effect on hepatic 6-phosphogluconate dehydrogenase activity.

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The effects of exogenous testosterone on spatial memory in rats

Open Life Sciences ◽

10.2478/s11535-010-0037-x ◽

2010 ◽

Vol 5 (4) ◽

pp. 466-471 ◽

Cited By ~ 2

Author(s):

Július Hodosy ◽

Ján Páleš ◽

Daniela Ostatníková ◽

Peter Celec

Keyword(s):

Spatial Memory ◽

Reference Memory ◽

Female Rats ◽

Male Rats ◽

Negative Effects ◽

Women Studies ◽

Male And Female Rats ◽

Low Testosterone ◽

Dose Dependent ◽

Estradiol Levels

AbstractTestosterone (T) is known to affect spatial abilities in men and women. Studies focusing on this relationship showed that both endogenous variability of T and administration of exogenous T, altered mental rotation and spatial visualization. Organizational and activational effects of T can be separately identified. The aim of our study was to evaluate the activational effects of exogenous T on spatial memory in male and female rats. T was administered 3 times a week over a two week period in either 1 mg/kg for low testosterone group or 10 mg/kg for high testosterone group. The Morris water maze was performed to assess the rat’s working and reference spatial memory. T and estradiol levels were measured in plasma. Increase in plasma T levels was confirmed in the experimental groups in comparison to the control groups (receiving sterile oil, 3 times a week over a two week period). Low dose T impaired working, but improved reference memory in female rats. In male rats the negative effects of T (both doses) on reference memory were shown. This experiment showed that the activational effects of exogenous testosterone on spatial memory of rats were gender and dose-dependent.

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