Oestradiol influences on dopamine release from the nucleus accumbens shell: sex differences and the role of selective oestradiol receptor subtypes

Yoest, Katie E.; Cummings, Jennifer A.; Becker, Jill B.

doi:10.1111/bph.14531

Cited by 47 publications

(38 citation statements)

References 57 publications

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“…Estradiol has been proposed as a major hormone to facilitate sex differences. Specific to the caudate-putamen, estradiol promotes motor coordination (Becker et al, 1987; Schultz et al, 2009) and its enhancement of dopamine action is specific to females (Becker, 1990; Xiao and Becker, 1994; Yoest et al, 2014, 2018a). The role of dopamine in regulating MSN electrical properties suggests that MSN properties would likewise differ between males, females, and across the adult female hormone cycle (Nicola et al, 2000).…”

Section: Dopamine and Estradiol Are Part Of The Mechanism Underlyingmentioning

confidence: 99%

Biological Sex, Estradiol and Striatal Medium Spiny Neuron Physiology: A Mini-Review

Krentzel

Meitzen

2018

Front. Cell. Neurosci.

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The caudate-putamen, nucleus accumbens core and shell are important striatal brain regions for premotor, limbic, habit formation, reward, and other critical cognitive functions. Striatal-relevant behaviors such as anxiety, motor coordination, locomotion, and sensitivity to reward, all change with fluctuations of the menstrual cycle in humans and the estrous cycle in rodents. These fluctuations implicate sex steroid hormones, such as 17β-estradiol, as potent neuromodulatory signals for striatal neuron activity. The medium spiny neuron (MSN), the primary neuron subtype of the striatal regions, expresses membrane estrogen receptors and exhibits sex differences both in intrinsic and synaptic electrophysiological properties. In this mini-review, we first describe sex differences in the electrophysiological properties of the MSNs in prepubertal rats. We then discuss specific examples of how the human menstrual and rat estrous cycles induce differences in striatal-relevant behaviors and neural substrate, including how female rat MSN electrophysiology is influenced by the estrous cycle. We then conclude the mini-review by discussing avenues for future investigation, including possible roles of striatal-localized membrane estrogen receptors and estradiol.

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Section: Dopamine and Estradiol Are Part Of The Mechanism Underlyingmentioning

confidence: 99%

Biological Sex, Estradiol and Striatal Medium Spiny Neuron Physiology: A Mini-Review

Krentzel

Meitzen

2018

Front. Cell. Neurosci.

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“…E2 has potent modulatory effects on this system (Yoest et al, 2018a). For example, E2 enhances cocaine-, amphetamine-, and potassium-stimulated DA release in the striatum of rats and mice (Becker, 1990a, b;Thompson and Moss, 1994;Tobiansky et al, 2016;Yoest et al, 2018b), and potentiates ethanol-stimulated DA release in the prefrontal cortex of female rats (Dazzi et al, 2007). In accord with this finding, ethanol-induced excitation of ventral tegmental area (VTA) DA neurons in female mice is augmented when E2 levels are elevated (Vandegrift et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor α Regulates Ethanol Excitation of Ventral Tegmental Area Neurons and Binge Drinking in Female Mice

Vandegrift

Hilderbrand

Satta

et al. 2019

Preprint

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Elevations in estrogen (17b-estradiol, E2) are associated with increased alcohol drinking by women and experimentally in rodents. E2 alters the activity of the dopamine system, including the ventral tegmental area (VTA) and its projection targets, which plays an important role in binge drinking. A previous study demonstrated that during high E2 states, VTA dopamine neurons in female mice are more sensitive to ethanol excitation. However, the mechanisms responsible for the ability of E2 to enhance ethanol sensitivity of VTA dopamine neurons have not been investigated. In this study, we used selective agonists and antagonists to examine the role of estrogen receptor subtypes (ERa and ERb) in regulating the ethanol sensitivity of VTA dopamine neurons and found that ERa promotes the enhanced ethanol response of VTA dopamine neurons. We also demonstrated that the E2-induced increase in ethanol excitation requires the activity of the metabotropic glutamate receptor, mGluR1, which is known to couple with ERa at the plasma membrane. To investigate the behavioral relevance of these findings, we administered lentivirus expressing short hairpin RNAs targeting either ERa or ERb into the VTA and found that knockdown of each receptor in the VTA reduced binge-like ethanol drinking in female, but not male, mice. Reducing ERa in the VTA had a more dramatic effect on binge-like drinking than reducing ERb, consistent with the ability of ERa to alter ethanol sensitivity of dopamine neurons. These results provide important insight into sex-specific mechanisms that drive excessive alcohol drinking. Significance StatementEstrogen has potent effects on the dopamine system and increases the vulnerability of females to develop addiction to substances such as cocaine and alcohol. We investigated the mechanisms by which estrogen increases the response of dopamine neurons in the ventral tegmental area to ethanol. We found that activation of the estrogen receptor, ERa, increased the ethanol-induced excitation of dopamine neurons and that this required the metabotropic glutamate receptor mGluR1. We also demonstrated that estrogen receptors in the ventral tegmental area regulate binge-like alcohol drinking by female, but not male, mice. The influence of estrogen receptors on binge drinking in female mice suggests that treatments for alcohol use disorder in women may need to account for this sex difference.

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“…Previous findings have implicated the ventral striatum as an important brain region for the rewarding effects of cocaine in females. Treatment of E2 acutely enhanced stimulated DA release after cocaine administration in female but not male rats (Yoest et al, 2018a). Our pilot studies did investigate the effect of ICI in the nucleus accumbens but did not see an effect on cocaine CPP.…”

Section: Discussionmentioning

confidence: 92%

“…However, there was no direct effect of E2 treatment on DA levels upon cocaine administration for intact or castrated male rats (Cummings et al, 2014). In the ventral striatum, E2 treatment acutely increases the effect of cocaine on stimulated DA release in female but not male rats (Yoest et al, 2018a).…”

Section: Introductionmentioning

confidence: 85%

Activation of G-protein coupled estradiol receptor 1 in the dorsolateral striatum attenuates preference for cocaine and saccharin in male but not female rats

Becker

2019

Preprint

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There 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.

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Oestradiol influences on dopamine release from the nucleus accumbens shell: sex differences and the role of selective oestradiol receptor subtypes

Cited by 47 publications

References 57 publications

Biological Sex, Estradiol and Striatal Medium Spiny Neuron Physiology: A Mini-Review

Biological Sex, Estradiol and Striatal Medium Spiny Neuron Physiology: A Mini-Review

Estrogen Receptor α Regulates Ethanol Excitation of Ventral Tegmental Area Neurons and Binge Drinking in Female Mice

Activation of G-protein coupled estradiol receptor 1 in the dorsolateral striatum attenuates preference for cocaine and saccharin in male but not female rats

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