Rapid effects of ovarian hormones in dorsal striatum and nucleus accumbens

Yoest, Katie E.; Quigley, Jacqueline; Becker, Jill B.

doi:10.1016/j.yhbeh.2018.04.002

Cited by 137 publications

(134 citation statements)

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“…Three subjects dropped out of the study due to illness or personal reasons, two after the initial baseline session and one after the first fMRI session. Only males were included, as female sex hormones fluctuate during menstrual cycle which may affect DA signaling (Almey, Milner, & Brake, 2015;Yoest, Quigley, & Becker, 2018). Participants were recruited online and included mainly university students.…”

Section: Participantsmentioning

confidence: 99%

Dopaminergic modulation of the exploration/exploitation trade-off in human decision-making

Chakroun

Mathar

Wiehler

et al. 2019

Preprint

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Acknowledgements: This work was funded by Deutsche Forschungsgemeinschaft (grant PE1627/5-1 to J.P.). Large parts of this publication are based on the dissertation "Dopaminergic modulation of the explore/exploit trade-off in human decision making" by K.C. (Chakroun, Karima: Dopaminergic modulation of the explore/exploit trade-off in human decision making [online]; Hamburg, Univ., Diss., 2019; Summary A central issue in reinforcement learning and decision-making is whether to exploit knowledge of reward values, or to explore novel options. Although it is widely hypothesized that dopamine neurotransmission plays a key role in regulating this balance, causal evidence for a role of dopamine in human exploration is still lacking. Here, we use a combination of computational modeling, pharmacological intervention and functional magnetic resonance imaging (fMRI) to test for a causal effect of dopamine transmission on the exploration-exploitation trade-off in humans. 31 healthy male subjects performed a restless four-armed bandit task in a within-subjects design under three drug conditions: 150mg of the dopamine precursor L-dopa, 2mg of the D2 receptor antagonist haloperidol, and placebo. In all conditions, choice behavior was best explained by an extension of an established Bayesian learning model accounting for perseveration, uncertainty-based exploration and random exploration. Uncertainty-based exploration was attenuated under L-dopa compared to placebo and haloperidol. There was no evidence for a modulation of prediction error signaling or categorical effects of exploration/exploitation under L-dopa, whereas model-based fMRI revealed that L-dopa attenuated neural representations of overall uncertainty in insula and dorsal anterior cingulate cortex. Our results highlight the computational role of these regions in exploration and suggest that dopamine modulates exploration by modulating how this circuit tracks accumulating uncertainty during decision-making.

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Section: Participantsmentioning

confidence: 99%

Dopaminergic modulation of the exploration/exploitation trade-off in human decision-making

Chakroun

Mathar

Wiehler

et al. 2019

Preprint

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“…Within the dorsal striatum, oestradiol acutely enhances dopamine release in females but not in males (Cummings et al ., ; Shams et al ., ). A substantial body of work has demonstrated that oestradiol acts directly on GABAergic striatal tissue to disinhibit dopaminergic terminals and promote dopamine release within the striatum (Yoest et al ., ). However, while the effects of oestradiol in dorsal striatum have been well established, studies on the rapid effects of oestradiol on dopamine release within the nucleus accumbens (NAc) have produced mixed results.…”

Section: Introductionmentioning

confidence: 97%

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

Yoest

Cummings

Becker

2018

British J Pharmacology

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Background and Purpose Females are more sensitive than males to both the acute and prolonged effects of psychomotor stimulants. In females, this is regulated by oestradiol, which enhances dopamine release in the dorsal striatum. In this study, we tested the acute effect of oestradiol on dopamine release in the nucleus accumbens (NAc) shell after cocaine administration and investigated which oestradiol receptors (ERs) contribute to sex differences in the response to cocaine. Experimental Approach The ability of oestradiol benzoate (EB) to acutely modulate the effect of cocaine on phasic dopamine release in the NAc shell was measured by fast‐scan cyclic voltammetry in anaesthetized male and female rats. The roles of ER subtypes, ERα and ERβ, was determined with selective agonists. Key Results EB acutely enhanced the effect of cocaine on stimulated dopamine release from the NAc shell in females but not in male rats only at levels of stimulation expected to optimally saturate dopamine transporters. Enhanced dopamine release after cocaine administration was also observed in females after selective activation of ERβ but not ERα. EB attenuated the effect of cocaine on NAc shell dopamine reuptake in males but not in females. Conclusions and Implications Oestradiol acutely and rapidly regulates dopamine release in females and dopamine reuptake in males. In females, oestradiol rapidly enhances the effect of cocaine on dopamine release, likely via activation of ERβ. The effect of oestradiol in males is not seen with selective receptor subtype activation, a topic deserving of further study. LINKED ARTICLES This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc

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“…The mesocorticolimbic dopamine (DA) system is critical for the rewarding and reinforcing effects of ethanol (Gonzales et al, 2004;Lovinger and Alvarez, 2017). 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).…”

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

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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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Rapid effects of ovarian hormones in dorsal striatum and nucleus accumbens

Cited by 137 publications

References 104 publications

Dopaminergic modulation of the exploration/exploitation trade-off in human decision-making

Dopaminergic modulation of the exploration/exploitation trade-off in human decision-making

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

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

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