scholarly journals G-protein coupled estradiol receptor 1 in dorsolateral striatum modulates cocaine preference in male rats

2019 ◽  
Author(s):  
Jacqueline A. Quigley ◽  
Jill B. Becker
Keyword(s):  
Sex Differences ◽  
Addiction Treatment ◽  
Cultural Influences ◽  
Protective Role ◽  
Gonadal Hormones ◽  
Male Rats ◽  
Estradiol Treatment ◽  
Drug Seeking ◽  
Dorsolateral Striatum ◽  
Estradiol Receptor

AbstractThere are sex differences in susceptibility to addiction. Cultural influences play a role in drug seeking behaviors; however, sex differences are found in rodent models of addiction as well, suggesting that there are also neurobiological factors involved. Extensive research has shown that estradiol facilitates enhanced motivation and drug seeking in female but not male rodents. Estradiol treatment also potentiates cocaine induced dopamine overflow in the dorsolateral striatum (DLS) of females. Together, these findings suggest that estradiol potentiates the rewarding effects of cocaine in females only. However, testosterone is aromatized to estradiol in the male brain but thus far, it’s action in males is not well understood. These studies used pharmacological treatments to manipulate ERα, ERβ and GPER1 in the DLS to investigate how estradiol receptors regulate preference for cocaine in both sexes. Antagonism of ERα or ERβ did not alter cocaine CPP in males, but GPER1 activation blocked cocaine preference and inhibition of GPER1 enhanced cocaine CPP in males. Surprisingly, there was no effect of GPER1 activation in females. There were no sex differences in relative mRNA expression of ERα, ERβ and GPER1 in the dorsal striatum. Together, these results indicate that estradiol is playing differential roles in males and females such that it may be protective against drug seeking in male rats while enhancing it in females.Significance StatementDrug addiction effects men and women differently but the way we treat addiction is not tailored by sex like it should be. Apart from cultural influence, one reason for sex differences in drug taking could be due to differences in neurobiological function and actions of gonadal hormones. This research article identifies a novel, protective, role for estradiol receptor, GPER1, in male rats only. This discovery could lead to sex-specific therapeutic targets for addiction treatment.

scholarly journals Risk-based Decision Making in Rats: Modulation by Sex and Amphetamine

2020 ◽  
Author(s):  
Dannia Islas-Preciado ◽  
Steven R. Wainwright ◽  
Julia Sniegocki ◽  
Stephane E. Lieblich ◽  
Shunya Yagi ◽  
...  
Keyword(s):  
Decision Making ◽  
Sex Differences ◽  
Gonadal Hormones ◽  
Risky Choice ◽  
Female Rats ◽  
Male Rats ◽  
Risky Decision Making ◽  
Risky Decision ◽  
17Β Estradiol ◽  
Males And Females

AbstractDecision-making is a complex process essential to daily adaptation in many species. Risk is an inherent aspect of decision-making and it is influenced by gonadal hormones. Testosterone and 17β-estradiol may modulate decision making and impact the mesocorticolimbic dopamine pathway. Here, we explored sex differences, the effect of gonadal hormones and the dopamine agonist amphetamine on risk-based decision making. Intact or gonadectomised (GDX) male and female rats underwent to a probabilistic discounting task. High and low doses of testosterone propionate (1.0 or 0.2 mg) and 17β-estradiol benzoate (0.3 μg) were administered to assess acute effects on risk-based decision making. After 3-days of washout period, intact and GDX rats received high or low (0.5 or 0.125 mg/kg) doses of amphetamine and re-tested in the probabilistic discounting task. Under baseline conditions, males made more risky choices during probability discounting compared to female rats, particularly in the lower probability blocks, but GDX did not influence risky choice. The high, but not the low dose, of testosterone modestly reduced risky decision making in GDX male rats. Conversely, 17β-estradiol had no significant effect on risky choice regardless of GDX status in either sex. Lastly, a higher dose of amphetamine increased risky decision making in both intact males and females, but had no effect in GDX rats. These findings demonstrated sex differences in risk-based decision making, with males showing a stronger bias towards larger, uncertain rewards. GDX status influenced the effects of amphetamine, suggesting different dopaminergic regulation in risk-based choices among males and females.

scholarly journals Activation of G-protein Coupled Estradiol Receptor 1 in the Dorsolateral Striatum Enhances Motivation for Cocaine and Drug-Induced Reinstatement in Female Rats

2021 ◽  
Author(s):  
Jacqueline Quigley ◽  
Molly K. Logsdon ◽  
Brianna C. Graham ◽  
Kendra G. Beaudoin ◽  
Jill B Becker
Keyword(s):  
G Protein ◽  
Progressive Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Ratio Schedule ◽  
Drug Induced ◽  
Drug Seeking ◽  
Schedule Of Reinforcement ◽  
Estradiol Receptor ◽  
G Protein Coupled

Abstract BackgroundEstradiol potentiates drug-taking behaviors, including motivation to self-administer cocaine and reinstatement of drug-seeking after extinction in females, but not males. The dorsolateral stratum (DLS) is a region of the brain implicated in mediating drug-seeking behaviors and more specifically, is a target brain area to study how estradiol regulates these behaviors. The estradiol receptors α, β, and G-protein coupled estradiol receptor 1 (GPER1) are all present in the DLS. In this study the effects of activating GPER1 in the DLS on drug-seeking are investigated. MethodsGonad-intact male and female rats were trained to self-administer cocaine (0.4 mg/kg/inf) on an fixed-ratio 1 schedule of reinforcement. For four weeks, animals underwent testing on a progressive ratio schedule of reinforcement to determine their motivation to attain cocaine. Halfway through progressive ratio testing, a selective agonist targeting GPER1 (G1) was administered intra-DLS to determine the contribution of GPER1 activation on motivation for cocaine. The effects of intra-GPER1 activation on drug-induced reinstatement after extinction was subsequently determined. ResultsActivation of GPER1, via G1 administration intra-DLS potentiated females’ motivation to self-administer cocaine. There was no effect of prior G1 treatment on extinction of cocaine-taking in females, however, G1 treatment resulted in greater drug-induced reinstatement (10 mg/kg cocaine, i.p.). There were no effects of intra-DLS GPER1 activation observed on motivation for cocaine or cocaine-induced reinstatement of responding in males. Conclusions These results support the conclusion that activation of GPER1 in the DLS enhances cocaine seeking behaviors for female, but not male rats.

scholarly journals Testicular hormones mediate robust sex differences in impulsive choice in rats

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Caesar M Hernandez ◽  
Caitlin Orsini ◽  
Alexa-Rae Wheeler ◽  
Tyler W Ten Eyck ◽  
Sara M Betzhold ◽  
...  
Keyword(s):  
Gender Differences ◽  
Sex Differences ◽  
Psychiatric Disorders ◽  
Intertemporal Choice ◽  
Gonadal Hormones ◽  
Male Rats ◽  
Food Motivation ◽  
Impulsive Choice ◽  
Biological Sex ◽  
Neuropsychiatric Conditions

Impairments in choosing optimally between immediate and delayed rewards are associated with numerous psychiatric disorders. Such ‘intertemporal’ choice is influenced by genetic and experiential factors; however, the contributions of biological sex are understudied and data to date are largely inconclusive. Rats were used to determine how sex and gonadal hormones influence choices between small, immediate and large, delayed rewards. Females showed markedly greater preference than males for small, immediate over large, delayed rewards (greater impulsive choice). This difference was neither due to differences in food motivation or reward magnitude perception, nor was it affected by estrous cycle. Ovariectomies did not affect choice in females, whereas orchiectomies increased impulsive choice in males. These data show that male rats exhibit less impulsive choice than females and that this difference is at least partly maintained by testicular hormones. These differences in impulsive choice could be linked to gender differences across multiple neuropsychiatric conditions.

scholarly journals Activation of G protein-coupled estradiol receptor 1 in the dorsolateral striatum enhances motivation for cocaine and drug-induced reinstatement in female but not male rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jacqueline A. Quigley ◽  
Molly K. Logsdon ◽  
Brianna C. Graham ◽  
Kendra G. Beaudoin ◽  
Jill B. Becker
Keyword(s):  
G Protein ◽  
Progressive Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Ratio Schedule ◽  
Drug Induced ◽  
Drug Seeking ◽  
Schedule Of Reinforcement ◽  
Estradiol Receptor ◽  
G Protein Coupled

Abstract Background Estradiol potentiates drug-taking behaviors, including motivation to self-administer cocaine and reinstatement of drug-seeking after extinction in females, but not males. The dorsolateral stratum (DLS) is a region of the brain implicated in mediating drug-seeking behaviors and, more specifically, is a target brain area to study how estradiol regulates these behaviors. The estradiol receptors α, β, and G protein-coupled estradiol receptor 1 (GPER1) are all present in the DLS. In this study, the effects of activating GPER1 in the DLS on drug-seeking are investigated. Methods Gonad-intact male and female rats were trained to self-administer cocaine (0.4 mg/kg/inf) on a fixed-ratio 1 schedule of reinforcement. For 4 weeks, animals underwent testing on a progressive ratio schedule of reinforcement to determine their motivation to attain cocaine. Halfway through progressive ratio testing, a selective agonist targeting GPER1 (G1) was administered intra-DLS to determine the contribution of GPER1 activation on motivation for cocaine. The effects of intra-DLS GPER1 activation on drug-induced reinstatement after extinction were subsequently determined. Results Activation of GPER1, via intra-DLS G1 administration, potentiated females’ motivation to self-administer cocaine. There was no effect of prior G1 treatment on extinction of cocaine-taking in females; however, G1 treatment resulted in greater drug-induced reinstatement (10 mg/kg cocaine, i.p.). There were no effects of intra-DLS GPER1 activation observed on motivation for cocaine or cocaine-induced reinstatement of responding in males. Conclusions These results support the conclusion that activation of GPER1 in the DLS enhances cocaine-seeking behaviors for female, but not male rats.

scholarly journals Mast Cells in the Developing Brain Determine Adult Sexual Behavior

2017 ◽  
Author(s):  
Kathryn M. Lenz ◽  
Lindsay A. Pickett ◽  
Christopher L. Wright ◽  
Katherine T. Davis ◽  
Anabel Galan ◽  
...  
Keyword(s):  
Mast Cell ◽  
Sex Differences ◽  
Mast Cells ◽  
Copulatory Behavior ◽  
Cell Number ◽  
Gonadal Hormones ◽  
Male Rats ◽  
Sex Behavior ◽  
Mast Cell Number ◽  
Brain And Behavior

AbstractSex differences in brain and behavior are programmed during development by gonadal hormones. We found that the immune system-derived mast cell is a primary target for the masculinizing hormone, estradiol. Male rats had more mast cells in the preoptic area (POA), a brain region essential for male copulatory behavior, during the critical period for sexual differentiation. Activating mast cells in females masculinized POA neuronal and microglial morphology and adult sex behavior, and inhibiting mast cells in males blunted masculinization. Estradiol increased mast cell number and caused mast cells to release histamine, which stimulated microglia to release prostaglandins and thereby induced male-typical synaptic patterning. Inducing an allergic reaction in pregnant dams increased mast cell number in the brains of female fetuses and masculinized neuronal and microglia morphology and adult copulatory behavior. These findings identify a novel non-neuronal origin of brain sex differences and non-steroidal source of variability in brain feminization.

scholarly journals Sex differences in addiction

2016 ◽  
Vol 18 (4) ◽  
pp. 395-402 ◽  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Sex Difference ◽  
Dopamine Release ◽  
Drugs Of Abuse ◽  
Female Rats ◽  
Neural Systems ◽  
Estradiol Treatment ◽  
Dorsolateral Striatum ◽  
Withdrawal Response

Women exhibit more rapid escalation from casual drug taking to addiction, exhibit a greater withdrawal response with abstinence, and tend to exhibit greater vulnerability than men in terms of treatment outcome. In rodents, short-term estradiol intake in female rats enhances acquisition and escalation of drug taking, motivation for drugs of abuse, and relapse-like behaviors. There is also a sex difference in the dopamine response in the nucleus accumbens. Ovariectomized female rats exhibit a smaller initial dopamine increase after cocaine treatment than castrated males. Estradiol treatment of ovariectomized female rats enhances stimulated dopamine release in the dorsolateral striatum, but not in the nucleus accumbens, resulting in a sex difference in the balance between these two dopaminergic projections. In the situation where drug-taking behavior becomes habitual, dopamine release has been reported to be enhanced in the dorsolateral striatum and attenuated in the nucleus accumbens. The sex difference in the balance between these neural systems is proposed to underlie sex differences in addiction.

The traditional sexual script and humor in courtship

2020 ◽  
Vol 33 (2) ◽  
pp. 197-218
Author(s):  
Elaina M. Ross ◽  
Jeffrey A. Hall
Keyword(s):  
Sex Differences ◽  
Gender Roles ◽  
Cultural Influences ◽  
Past Research ◽  
Ambivalent Sexism ◽  
Hostile Sexism ◽  
Sexual Script ◽  
Biological Sex ◽  
Sex Influence ◽  
Potential Partner

AbstractTo account for sex differences in the production, receptivity, and preference for humor in potential mates during courtship, past research has often adopted an evolutionary approach. The present manuscript will attempt to integrate evolutionary explanations with proximal social and cultural influences using the traditional sexual script and ambivalent sexism theory. The results of both Study 1 (N=227) and Study 2 (N=424) suggest that trait masculinity is positively associated with humor production in courtship, while trait femininity is associated with humor receptivity. Study 1 indicated that the traditional flirting style was associated with less humor production by women, and Study 2 indicated that hostile sexism was related to a lower preference for a humor-producing potential partner by men. A sex difference in humor production in potential partners in Study 2 was no longer detectable once trait gender and hostile sexism was accounted for. Taken together, gender roles, over and above biological sex, influence one’s own humor use in courtship and preference for humor in potential partners.

scholarly journals Sex-Specific Differences in Glioblastoma

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1783
Author(s):  
Anna Carrano ◽  
Juan Jose Juarez ◽  
Diego Incontri ◽  
Antonio Ibarra ◽  
Hugo Guerrero Cazares
Keyword(s):  
Sex Differences ◽  
Immune System ◽  
Molecular Level ◽  
Deep Understanding ◽  
Protective Role ◽  
Men And Women ◽  
Individualized Approach ◽  
Male Patients ◽  
Outcome Differences

Sex differences have been well identified in many brain tumors. Even though glioblastoma (GBM) is the most common primary malignant brain tumor in adults and has the worst outcome, well-established differences between men and women are limited to incidence and outcome. Little is known about sex differences in GBM at the disease phenotype and genetical/molecular level. This review focuses on a deep understanding of the pathophysiology of GBM, including hormones, metabolic pathways, the immune system, and molecular changes, along with differences between men and women and how these dimorphisms affect disease outcome. The information analyzed in this review shows a greater incidence and worse outcome in male patients with GBM compared with female patients. We highlight the protective role of estrogen and the upregulation of androgen receptors and testosterone having detrimental effects on GBM. Moreover, hormones and the immune system work in synergy to directly affect the GBM microenvironment. Genetic and molecular differences have also recently been identified. Specific genes and molecular pathways, either upregulated or downregulated depending on sex, could potentially directly dictate GBM outcome differences. It appears that sexual dimorphism in GBM affects patient outcome and requires an individualized approach to management considering the sex of the patient, especially in relation to differences at the molecular level.

Fetuin-A exerts a protective effect against experimentally induced intestinal ischemia/reperfusion by suppressing autophagic cell death

2021 ◽  
pp. 153537022199520
Author(s):  
Nanees F El-Malkey ◽  
Amira E Alsemeh ◽  
Wesam MR Ashour ◽  
Nancy H Hassan ◽  
Husam M Edrees
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Beclin 1 ◽  
Male Rats ◽  
Fetuin A ◽  
Intestinal Ischemia Reperfusion ◽  
And Oxidative Stress

Intestinal tissue is highly susceptible to ischemia/reperfusion injury in many hazardous health conditions. The anti-inflammatory and antioxidant glycoprotein fetuin-A showed efficacy in cerebral ischemic injury; however, its protective role against intestinal ischemia/reperfusion remains elusive. Therefore, this study investigated the protective role of fetuin-A supplementation against intestinal structural changes and dysfunction in a rat model of intestinal ischemia/reperfusion. We equally divided 72 male rats into control, sham, ischemia/reperfusion, and fetuin-A-pretreated ischemia/reperfusion (100 mg/kg/day fetuin-A intraperitoneally for three days prior to surgery and a third dose 1 h prior to the experiment) groups. After 2 h of reperfusion, the jejunum was dissected and examined for spontaneous contractility. A jejunal homogenate was used to assess inflammatory and oxidative stress enzymes. Staining of histological sections was carried out with hematoxylin, eosin and Masson’s trichrome stain for evaluation. Immunohistochemistry was performed to detect autophagy proteins beclin-1, LC3, and p62. This study found that fetuin-A significantly improved ischemia/reperfusion-induced mucosal injury by reducing the percentage of areas of collagen deposition, increasing the amplitude of spontaneous contraction, decreasing inflammation and oxidative stress, and upregulating p62 expression, which was accompanied by beclin-1 and LC3 downregulation. Our findings suggest that fetuin-A treatment can prevent ischemia/reperfusion-induced jejunal structural and functional changes by increasing antioxidant activity and regulating autophagy disturbances observed in the ischemia/reperfusion rat model. Furthermore, fetuin-A may provide a protective influence against intestinal ischemia/reperfusion complications.

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