Sex dimorphisms in the 3D cytoarchitecture of the adult VTA and permanent alterations by glucocorticoid exposure in late gestation

Gillies, G; McArthur, Simon; McHale, Emily

doi:10.1016/j.yfrne.2006.03.219

Cited by 3 publications

(3 citation statements)

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“…Sex differences are also observed in within the mesolimbic DA system. DA neurons are larger and more abundant in the VTA of females compared to males 33,34 . Moreover, females have higher rates of DA release and reuptake in the NAc, which can be sensitive to circulating ovarian hormones [35][36][37] .…”

Section: Introductionmentioning

confidence: 93%

Time-dependent enhancement in ventral tegmental area dopamine neuron activity drives pain-facilitated fentanyl intake in males

Higginbotham

Abt

Teich

et al. 2022

Preprint

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Pain affects over 50% of US adults. Opioids are potent analgesics used to treat pain symptoms but are highly prone to abuse, creating a major dilemma for public health. Evidence suggests that the proclivity for opioid abuse under pain conditions varies between sexes. However, the neural mechanisms underlying sex-specific effects of pain on opioid use are largely unclear. Here, we recapitulate clinical findings and demonstrate that pain increases self-administration of the widely abused opioid, fentanyl, selectively in male rats. These behavioral effects develop over time and are paralleled by sex- and pain-specific effects on fentanyl-evoked ventral tegmental area (VTA) dopamine (DA) neuron activity, a critical mediator of motivation and reward. Using in vivo fiber photometry, we show that tonic VTA DA neuron activity is attenuated in males with pain. In contrast, phasic VTA DA neuron responses to self-administered fentanyl increase in magnitude at later timepoints and correspond with increases in fentanyl intake. The protracted increase in fentanyl-evoked VTA DA activity is necessary for pain to enhance fentanyl self-administration in males because chemogenetic inhibition of VTA DA neurons normalized fentanyl intake and associated fentanyl-evoked VTA DA neuron responses. These findings reveal time-dependent and sex-specific pain-induced adaptations to VTA DA neuron function that underlie maladaptive patterns of opioid use.

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Section: Introductionmentioning

confidence: 93%

Time-dependent enhancement in ventral tegmental area dopamine neuron activity drives pain-facilitated fentanyl intake in males

Higginbotham

Abt

Teich

et al. 2022

Preprint

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“…Further, in the VTA, dopamine neurons make up a larger percentage of the cellular population in females [7]. Finally, morphologically, VTA soma in females are larger compared to males [14]. These neuroanatomical differences serve as a critical substrate upon which subsequent hormonal regulation or stimulus-specific excitation can act to elicit and regulate dopamine release in males and females.…”

Section: Hormone-dependent Effects On Dopamine Release In the Striatummentioning

confidence: 99%

“…Many of these disorders are characterized by dysfunction in the dopamine system in reward-related brain regions [3,4], and as such, there has been considerable interest in outlining the sex differences in dopaminergic anatomy, regulation, and function in preclinical models. Many sex differences exist independent of ovarian cycle fluctuations and reflect differences in basal dopamine system organization/neuroanatomy [5][6][7][8][9][10][11][12][13][14]. In addition, there is also robust dopamine system regulation by ovarian hormones where hormones, such as 17β-estradiol (E2), increase dopamine cell activity and release from dopamine terminals in the striatum [15].…”

Section: Introductionmentioning

confidence: 99%

Sex differences in dopamine release regulation in the striatum

Zachry

Nolan

Brady

et al. 2020

Neuropsychopharmacol.

102

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The mesolimbic dopamine system-which originates in the ventral tegmental area and projects to the striatum-has been shown to be involved in the expression of sex-specific behavior and is thought to be a critical mediator of many psychiatric diseases. While substantial work has focused on sex differences in the anatomy of dopamine neurons and relative dopamine levels between males and females, an important characteristic of dopamine release from axon terminals in the striatum is that it is rapidly modulated by local regulatory mechanisms independent of somatic activity. These processes can occur via homosynaptic mechanisms-such as presynaptic dopamine autoreceptors and dopamine transporters-as well as heterosynaptic mechanisms, such as retrograde signaling from postsynaptic cholinergic and GABAergic systems, among others. These regulators serve as potential targets for the expression of sex differences in dopamine regulation in both ovarian hormone-dependent and independent fashions. This review describes how sex differences in microcircuit regulatory mechanisms can alter dopamine dynamics between males and females. We then describe what is known about the hormonal mechanisms controlling/regulating these processes. Finally, we highlight the missing gaps in our knowledge of these systems in females. Together, a more comprehensive and mechanistic understanding of how sex differences in dopamine function manifest will be particularly important in developing evidence-based therapeutics that target this system and show efficacy in both sexes.

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Alzheimer’s Disease and Sex-Dependent Alterations in the Striatum: A Lesson from a Mouse Model

Barbera

D’Amelio

2023

JAD

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In the last years, many clinical studies highlighted sex-specific differences in the pathophysiology of Alzheimer’s disease (AD). The recent paper published in the Journal of Alzheimer’s Disease shows the influence of sex on amyloid-β plaque deposition, behavior, and dopaminergic signaling in the 5xFAD mouse model of AD, with worse alterations in female mice. This commentary focuses on the importance of recognizing sex as a key variable to consider for a more precise clinical practice, with the challenge to develop sex-specific therapeutic interventions in neurodegenerative diseases such as AD.

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Sex dimorphisms in the 3D cytoarchitecture of the adult VTA and permanent alterations by glucocorticoid exposure in late gestation

Cited by 3 publications

References 0 publications

Time-dependent enhancement in ventral tegmental area dopamine neuron activity drives pain-facilitated fentanyl intake in males

Time-dependent enhancement in ventral tegmental area dopamine neuron activity drives pain-facilitated fentanyl intake in males

Sex differences in dopamine release regulation in the striatum

Alzheimer’s Disease and Sex-Dependent Alterations in the Striatum: A Lesson from a Mouse Model

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