Sex Differences in Demand for Highly Palatable Foods: Role of the Orexin System

Abstract Background The prevalence of eating disorders, including binge eating disorder, is significantly higher in women. These findings are mirrored by preclinical studies, which indicate that female rats have a higher preference for palatable food and show greater binge-like eating compared with male rats. Methods Here, we describe a novel within-session behavioral-economic paradigm that allows for the simultaneous measurement of the intake at null cost (Q0) and normalized demand elasticity (α) of 3 types of palatable food (low fat, high fat, and chocolate sucrose pellets) via demand curve analysis. In light of evidence that the orexin (hypocretin) system is critically involved in reward and feeding behaviors, we also examined the role of orexin function in sex differences of economic demand for palatable foods. Results The novel within-session behavioral-economic approach revealed that female rats have higher intake (demand) than males for all palatable foods at low cost (normalized to body weight) but no difference in intake at higher prices, indicating sex-dependent differences in the hedonic, but not motivational, aspects of palatable food. Immediately following behavioral-economic testing, we observed more orexin-expressing neurons and Fos expression (measure of recent neural activation) in these neurons in female rats compared with male rats. Moreover, the orexin-1 receptor antagonist SB334867 reduced both low- and high-cost intake for palatable food in both male and female rats. Conclusions These findings provide evidence of higher demand at low prices for palatable food in females and indicate that these behavioral differences may be associated with sexual dimorphism in orexin system function.

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Sex-specific effects of neonatal progestin receptor antagonism on juvenile social behavior in rats.

10.21203/rs.3.rs-649875/v1 ◽

2021 ◽

Author(s):

Robin M Forbes-Lorman

Keyword(s):

Sex Differences ◽

Brain Regions ◽

Female Rats ◽

Male Rats ◽

Postnatal Life ◽

Social Discrimination ◽

Specific Effects ◽

Male And Female Rats ◽

Brain And Behavior

Abstract Developing mammals are exposed to progesterone through several sources; however, the role of progesterone in early development is not well understood. Males express more progestin receptors (PRs) than females within several brain regions during early postnatal life, suggesting that PRs may be important for the organization of the sex differences in the brain and behavior. Indeed, previous studies showed cognitive impairments in male rats treated neonatally with a PR antagonist. In the present study, we examined the role of PRs in organizing juvenile behaviors. Social play behavior and social discrimination were examined in juvenile male and female rats that had been treated with CDB, a PR antagonist, during the first week of postnatal life. Interestingly, neonatal PR antagonism altered different juvenile behaviors in males and females. A transient disruption in PR signaling during development had no effect on social discrimination but increased play initiation and pins in females. These data suggest that PRs play an important role in the organization of sex differences in some social behaviors.

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Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis

Biology of Sex Differences ◽

10.1186/s13293-020-00346-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ming Song ◽

Fang Yuan ◽

Xiaohong Li ◽

Xipeng Ma ◽

Xinmin Yin ◽

...

Keyword(s):

Sex Differences ◽

Microbial Activity ◽

Hepatic Steatosis ◽

Female Rats ◽

Male Rats ◽

Calorie Intake ◽

Dietary Copper ◽

Male And Female ◽

Male And Female Rats ◽

Rrna Sequencing

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.

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Vulnerability factors for mephedrone-induced conditioned place preference in rats—the impact of sex differences, social-conditioning and stress

Psychopharmacology ◽

10.1007/s00213-021-05910-y ◽

2021 ◽

Author(s):

Olga Wronikowska ◽

Maria Zykubek ◽

Łukasz Kurach ◽

Agnieszka Michalak ◽

Anna Boguszewska-Czubara ◽

...

Keyword(s):

Sex Differences ◽

Conditioned Place Preference ◽

Low Dose ◽

Social Factor ◽

Place Preference ◽

Female Rats ◽

Male Rats ◽

Social Conditioning ◽

Male And Female Rats ◽

The Impact

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.

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Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyz050 ◽

2019 ◽

Vol 22 (11) ◽

pp. 710-723 ◽

Cited By ~ 8

Author(s):

Atul P Daiwile ◽

Subramaniam Jayanthi ◽

Bruce Ladenheim ◽

Michael T McCoy ◽

Christie Brannock ◽

...

Keyword(s):

Sex Differences ◽

Nucleus Accumbens ◽

Fixed Ratio ◽

Female Rats ◽

Male Rats ◽

Mrna Levels ◽

Self Administration ◽

Male And Female ◽

Orexin Receptors ◽

Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

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Similar levels of emotional contagion in male and female rats

10.1101/857094 ◽

2019 ◽

Author(s):

Yingying Han ◽

Bo Sichterman ◽

Maria Carrillo ◽

Valeria Gazzola ◽

Christian Keysers

Keyword(s):

Sex Differences ◽

Social Life ◽

Emotional Contagion ◽

Female Rats ◽

Male Rats ◽

Neural Basis ◽

Male And Female Rats ◽

Danger Detection ◽

Rats And Mice ◽

Shed Light

AbstractEmotional contagion, the ability to feel what other individuals feel, is thought to be an important element of social life. In humans, emotional contagion has been shown to be stronger in women than men. Emotional contagion has been shown to exist also in rodents, and a growing number of studies explore the neural basis of emotional contagion in male rats and mice. These studies promise to shed light on the mechanisms that might go astray in psychiatric disorders characterized by dysfunctions of emotional contagion and empathy. Here we explore whether there are sex differences in emotional contagion in rats. We use an established paradigm in which a demonstrator rat receives footshocks while freezing is measured in both the demonstrator and an observer rat, which can hear, smell and see each other. By comparing pairs of male rats with pairs of female rats, we find (i) that female demonstrators freeze less when submitted to footshocks, but that (ii) the emotional contagion response, i.e. the degree of influence across the rats, does not depend on the sex of the rats. This was true whether emotional contagion was quantified based on the slope of a regression linking demonstrator and observer average freezing, or on Granger causality estimates of moment-to-moment freezing. The lack of sex differences in emotional contagion is compatible with an interpretation of emotional contagion as serving selfish danger detection.

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Mesenteric vascular responses to vasopressin during development of DOCA-salt hypertension in male and female rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.1.r40 ◽

1995 ◽

Vol 268 (1) ◽

pp. R40-R49 ◽

Cited By ~ 6

Author(s):

J. N. Stallone

Keyword(s):

Sex Differences ◽

Acute Treatment ◽

Vascular Reactivity ◽

Chronic Treatment ◽

Female Rats ◽

Salt Treatment ◽

Male And Female Rats ◽

Salt Hypertension ◽

Vascular Responsiveness

Deoxycorticosterone acetate (DOCA)-salt hypertension develops to a greater extent in male (M) than in female (F) rats. To determine the role of the vasculature, reactivity to arginine vasopressin (AVP) and prostanoid output were examined in the isolated perfused mesenteric vasculature of hypertensive (HT) and normotensive-control (NTC) M and F rats after acute (1-wk) and chronic (4-wk) DOCA-salt treatment. Systolic blood pressure was significantly higher in M than in F HT rats (187 +/- 3 vs. 151 +/- 3 mmHg after 4 wk; P < 0.02). After acute treatment, vascular reactivity to AVP (maximal perfusion pressure) in HT was elevated in M (181 +/- 18 mmHg; P < 0.02) but not in F (135 +/- 6 mmHg) compared with NTC (90 +/- 6 mmHg, M vs. 119 +/- 5 mmHg, F). After chronic treatment, vascular reactivity to AVP in HT was elevated in both sexes (P < 0.02), although more in F (175 +/- 13 mmHg) than in M (141 +/- 11 mmHg). In contrast, vascular responsiveness to phenylephrine did not differ significantly between M and F NTC or HT preparations after either acute or chronic treatment. Sex differences in basal and AVP-induced 6-ketoprostaglandin (6-keto-PG) F1 alpha and PGE2 output by HT and NTC vasculature were reciprocal to sex differences in the vasoconstriction responses to AVP. After acute treatment, AVP-stimulated 6-keto-PGF1 alpha output by HT was elevated slightly in F (33.6 +/- 1.7 ng/3 min; P < or = 0.02) but not in M (49.9 +/- 4.3 ng/3 min) compared with NTC (23.5 +/- 2.6 ng/3 min, F vs. 34.7 +/- 4.9 ng/3 min, M). After chronic treatment, output by HT was enhanced in both sexes (P < or = to 0.02), although more in M (109 +/- 15.4 ng/3 min) than in F (68 +/- 6.6 ng/3 min)> These findings suggest that sex differences in the relative balance between AVP-induced vasoconstriction and vasodilatory prostanoid release may contribute to male-female differences in mesenteric vascular reactivity to AVP in NT and that disturbances in this balance may be responsible, at least in part, for the sex- and time-dependent changes in reactivity to AVP observed during the development of DOCA-salt hypertension.

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γ-Aminobutyric acid regulation of neurohypophysial hormone secretion in male and female rats

Journal of Endocrinology ◽

10.1677/joe.0.1210343 ◽

1989 ◽

Vol 121 (2) ◽

pp. 343-349 ◽

Cited By ~ 25

Author(s):

E. Saridaki ◽

D. A. Carter ◽

S. L. Lightman

Keyword(s):

Hormone Secretion ◽

Model Systems ◽

Female Rats ◽

Aminobutyric Acid ◽

Male Rats ◽

Sexually Dimorphic ◽

Male And Female ◽

Endogenous Gaba ◽

Male And Female Rats

ABSTRACT The role of γ-aminobutyric acid (GABA) in the control of oxytocin and arginine vasopressin (AVP) release from the posterior pituitary was investigated using the GABA agonist muscimol and the GABA antagonists bicuculline and picrotoxin. Two perifusion model systems were studied using (a) intact isolated posterior pituitaries (IPP) and (b) neurosecretosomes from both male and female rats. In experiments on tissue from male rats, the stimulated release of oxytocin and AVP in both models was inhibited by muscimol, an effect which was reversed in the presence of bicuculline. Bicuculline alone increased the release of oxytocin only. Although similar responses to muscimol or bicuculline were seen in neurosecretosomes from female animals, neither agent affected oxytocin and AVP release from the intact IPP. Picrotoxin had a similar effect to bicuculline on oxytocin in isolated posterior pituitaries from male as well as female rats, although at the neurosecretosome level a paradoxical inhibition was observed. These results provide evidence for an endogenous GABA receptor mechanism at the level of the neurosecretory terminals in both male and female rats. The sexually dimorphic IPP response suggests a second more complex mechanism involving either pituicytenerve terminal interactions and/or a secondary role of other neurotransmitters in the GABA regulation of neurohypophysial hormones. Journal of Endocrinology (1989) 121, 343–349

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Sex differences in ET-1 receptor expression and Ca2+ signaling in the IMCD

AJP Renal Physiology ◽

10.1152/ajprenal.00400.2013 ◽

2013 ◽

Vol 305 (8) ◽

pp. F1099-F1104 ◽

Cited By ~ 18

Author(s):

Chunhua Jin ◽

Joshua S. Speed ◽

Kelly A. Hyndman ◽

Paul M. O'Connor ◽

David M. Pollock

Keyword(s):

Sex Differences ◽

Radioligand Binding ◽

Collecting Duct ◽

Receptor Activation ◽

Receptor Expression ◽

Female Rats ◽

Male Rats ◽

Male And Female ◽

Male And Female Rats ◽

Intracellular Ca

The inner medullary collecting duct (IMCD) is the nephron segment with the highest production of endothelin-1 (ET-1) and the greatest expression of ET-1 receptors that function to adjust Na+ and water balance. We have reported that male rats have reduced natriuresis in response to direct intramedullary infusion of ET-1 compared with female rats. Our aim was to determine whether alterations of ET-1 receptor expression and downstream intracellular Ca2+ signaling within the IMCD could account for these sex differences. IMCDs from male and female rats were isolated for radioligand binding or microdissected for intracellular Ca2+ ([Ca2+]i) measurement by fluorescence imaging of fura-2 AM. IMCD from male and female rats had similar ETB expression (655 ± 201 vs. 567 ± 39 fmol/mg protein, respectively), whereas male rats had significantly higher ETA expression (436 ± 162 vs. 47 ± 29 fmol/mg protein, respectively; P < 0.05). The [Ca2+]i response to ET-1 was significantly greater in IMCDs from male compared with female rats (288 ± 52 vs. 118 ± 32 AUC, nM × 3 min, respectively; P < 0.05). In IMCDs from male rats, the [Ca2+]i response to ET-1 was significantly blunted by the ETA antagonist BQ-123 but not by the ETB antagonist BQ-788 (control: 137 ± 27; BQ-123: 53 ± 11; BQ-788: 84 ± 25 AUC, nM × 3 min; P < 0.05), consistent with greater ETA receptor function in male rats. These data demonstrate a sex difference in ETA receptor expression that results in differences in ET-1 Ca2+ signaling in IMCD. Since activation of ETA receptors is thought to oppose ETB receptor activation, enhanced ETA function in male rats could limit the natriuretic effects of ETB receptor activation.

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Potentiation by endothelin-1 and vasopressin of sympathetic vasoconstriction in male and female rats

Clinical Science ◽

10.1042/cs103s158s ◽

2002 ◽

Vol 103 (s2002) ◽

pp. 158S-161S ◽

Cited By ~ 1

Author(s):

Nuria FERNÁNDEZ ◽

Elena SANZ ◽

Luis MONGE ◽

María Angeles MARTÍNEZ ◽

Godofredo DIÉGUEZ ◽

...

Keyword(s):

Electrical Field Stimulation ◽

Female Rats ◽

Male Rats ◽

Electrical Field ◽

Endothelin 1 ◽

Male And Female Rats ◽

Sympathetic Vasoconstriction ◽

Arterial Contraction ◽

Rat Tail

The aim of this study was to analyse the modulatory role of endothelin-1 and vasopressin in sympathetic vasoconstriction, and whether there are gender differences in this modulatory role. Electrical field stimulation (4Hz, 0.2ms pulse duration at supramaximal voltage of 70V, for 1s), applied to isolated segments from rat tail arteries, produced a contraction that was lower in the vascular segments from female than in those from male rats. This arterial contraction was potentiated in a concentration-dependent way by endothelin-1 (10-10–3×10-9mol/l) and vasopressin (10-12–10-10mol/l), and the increment produced by endothelin-1 was similar in the arteries of both, whereas the increment induced by vasopressin was higher in the arteries from male than in those from female rats. These results suggest that endothelin-1 and vasopressin potentiate the vasoconstriction to sympathetic stimulation, and this potentiating effect of vasopressin may be higher, whereas that of endothelin-1 may be similar, in males than in females.

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Gonadal and sex steroid feedback regulation of gonadotrophin mRNA levels and secretion in neonatal male and female rats

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0030139 ◽

1989 ◽

Vol 3 (2) ◽

pp. 139-144 ◽

Cited By ~ 10

Author(s):

P. Pakarinen ◽

I. Huhtaniemi

Keyword(s):

Sex Differences ◽

Feedback Regulation ◽

Female Rats ◽

Male Rats ◽

Sex Steroid ◽

Mrna Levels ◽

Negative Feedback Regulation ◽

Α Subunit ◽

Male And Female ◽

Male And Female Rats

ABSTRACT Serum and pituitary LH and FSH, and their pituitary mRNA levels, were measured in neonatal male and female rats after gonadectomy and after gonadectomy with sex steroid replacement. The animals were gonadectomized on day 3 of life, and those given sex steroid replacement were implanted with silicone elastomer capsules containing testosterone for males and diethylstilboestrol for females. Shamoperated rats served as controls. The animals were killed 4 or 8 days later and the sera and pituitaries collected. Pituitary contents of mRNAs for the α subunit, FSH-β and LH-β were determined by blot hybridization using corresponding cDNAs. Distinct sex differences were found in the mRNA responses to gonadectomy and steroid replacement. In the males, gonadectomy increased all mRNA levels at 7 days of age. In the females, a rise on day 7 was detected only for FSH-β; the other mRNAs were increased on day 11 of age. The steroid replacements reversed all the post-gonadectomy increases of mRNAs in both sexes. Moreover, the common α and LH-β mRNAs of the male animals were consistently suppressed below control levels. The serum concentrations of gonadotrophins increased after gonadectomy on day 7 in the males but only on day 11 in the females. The steroid replacements also suppressed the post-gonadectomy increases in serum gonadotrophins, but only the serum concentration of FSH in the females was reduced below controls. Pituitary gonadotrophin concentrations were not affected by gonadectomy, but the steroids suppressed LH in the males and FSH in the females. It is concluded that the onset of negative-feedback regulation of gonadotrophin synthesis by gonads and/or gonadal steroids starts earlier in male rats, before 7 days of age. In female rats these responses appear between 7 and 11 days of age. Clear sex differences were observed in how gonadotrophin mRNAs and pituitary and serum hormone levels responded to gonadectomy and steroid replacement in the neonatal period. Some of the responses differed from those previously reported in adult animals.

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