Sex, Drugs, and the Medial Amygdala: A Model of Enhanced Sexual Motivation in the Female Rat

Rudzinskas, Sarah; Williams, Katrina; Mong, Jessica A.; Holder, Mary K.

doi:10.3389/fnbeh.2019.00203

Cited by 11 publications

(12 citation statements)

References 133 publications

(175 reference statements)

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“…Many of these genes are downregulated in meA by cocaine in GHF and SIM, and upregulated by cocaine in SIF. This may reflect an important sex-specific difference in second messenger signaling in response to dopamine within meA, as has been reported (Rudzinskas et al, 2019).…”

Section: Discussionsupporting

confidence: 51%

“…We focused on meA because of its known sex differences in size (Hines et al, 1992), transcription (Chen et al, 2019), development (De Lorme et al, 2012, mechanisms of sexual differentiation (Argue et al, 2017;Krebs-Kraft et al, 2010;Nugent et al, 2009;Zehr et al, 2006), importance in sex-specific reward-associated behaviors (Chen et al, 2019;Li et al, 2017;Unger et al, 2015) and sensitivity to adolescent stress (Cooke et al, 2000;Hodges et al, 2019). Additionally, while evidence suggests that meA is an important regulator of drug sensitivity in females (Rudzinskas et al, 2019), very little is known about males (Knapska et al, 2007). Therefore, we sought to broaden our understanding of baseline sex-specific transcriptional responses in meA to cocaine in addition to characterizing how those responses are affected by adolescent SI.…”

Section: Discussionmentioning

confidence: 99%

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Adolescent Social Isolation Reprograms the Medial Amygdala: Transcriptome and Sex Differences in Reward

Walker

Zhou

Ramakrishnan

et al. 2020

Preprint

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Adolescence is a sensitive window for reward-and stress-associated behavior. Although stress during this period causes long-term changes in behavior in males, how females respond is relatively unknown. Here we show that social isolation stress in adolescence, but not adulthood, induces persistent but opposite effects on anxiety-and cocaine-related behaviors in male vs. female mice, and that these effects are reflected in transcriptional profiles within the adult medial amygdala (meA). By integrating differential gene expression with co-expression network analyses, we identified crystallin mu (Crym), a thyroid-binding protein, as a key driver of these transcriptional profiles. Manipulation of Crym specifically within adult meA neurons recapitulates the behavioral and transcriptional effects of social isolation and re-opens a window of plasticity that is otherwise closed. Our results establish that meA is essential for sex-specific responses to stressful and rewarding stimuli through transcriptional programming that occurs during adolescence. INTRODUCTION:In many mammals, sex differences in behavior are required for the perpetuation of the species and are expressed as differences in mating and reproductive strategies. Individual variations in reproductive strategies are known to be dependent on e n v i r o n m e n t a l f a c t o r s a n d r e l y o n programming mediated by experiencedependent plasticity (Bergan et al., 2014). Stressful and rewarding stimuli are two key factors that may be especially important for encoding these strategies to optimize sexual behaviors and maximize reproductive success . However, very little is known about the brain region-specific m o l e c u l a r p r o c e s s e s u n d e r l y i n g t h e programming of such strategies.Adolescence is a sensitive period for programming reward-associated behaviors particularly in males (Sisk, 2016;Walker et al., 2019) and a time of heightened responsiveness to rewarding and stressful Statistical Analysis of Behavioral DataAll behaviors were analyzed using a 2-way ANOVA or a Kruskall-Wallis non-parametric test depending on the significance of a Levene's test for homogeneity of variance. If an interaction was identified, a Tukey post-hoc analysis was conducted to determine specific differences between groups. If an effect was identified via Kruskall-Wallis, follow-up Mann-Whitney tests were run to determine specific differences between groups. Chi-square tests were used to determine differences in the distribution of behavioral phenotypes within a group (marble burying and CPP). Pearson's Chi Squared tests were used to account for the lack of representation of all categories across groups. All analyses were conducted using SPSS Statistical Software, V25 (IBM, Armonk, NY). Cocaine Injections and Tissue Collection for RNA-seqOn P80, animals were divided into 8 groups of males and 8 groups of females: GH + chronic cocaine/saline; SI + chronic cocaine /saline; GH + acute cocaine/saline; SI + acute cocaine/saline. In total, 200 animals were utlilized. F...

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Adolescent Social Isolation Reprograms the Medial Amygdala: Transcriptome and Sex Differences in Reward

Walker

Zhou

Ramakrishnan

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Their repertoire of sexual behavior encompasses attractivity, proceptivity, and receptivity. Attractivity and proceptivity behaviors aim to solicit male mounting such as hopping, darting, and ear wiggling (reviewed in Micevych and Meisel, 2017;Rudzinskas et al, 2019). In response to male mounting, the female displays receptivity through arching their back, a behavior termed lordosis (reviewed in Micevych and Meisel, 2017).…”

Section: Rodent Female Sexual Behaviormentioning

confidence: 99%

“…Research on sexual behavior benefited greatly from rodent models, including the discovery of several brain regions important for sexual behavior (Snoeren et al, 2014;Rudzinskas et al, 2019). Within these regions, glutamate acts as a pivotal neurotransmitter for sexual behavior (reviewed in Hull and Dominguez, 2006;Dominguez, 2009;Will et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Glutamate in Male and Female Sexual Behavior: Receptors, Transporters, and Steroid Independence

Chiang

Park

2020

Front. Behav. Neurosci.

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The survival of animal species predicates on the success of sexual reproduction. Neurotransmitters play an integral role in the expression of these sexual behaviors in the brain. Here, we review the role of glutamate in sexual behavior in rodents and non-rodent species for both males and females. These encompass the release of glutamate and correlations with glutamate receptor expression during sexual behavior. We then present the effects of glutamate on sexual behavior, as well as the effects of antagonists and agonists on different glutamate transporters and receptors. Following that, we discuss the potential role of glutamate on steroid-independent sexual behavior. Finally, we demonstrate the interaction of glutamate with other neurotransmitters to impact sexual behavior. These sexual behavior studies are crucial in the development of novel treatments of sexual dysfunction and in furthering our understanding of the complexity of sexual diversity. In the past decade, we have witnessed the burgeoning of novel techniques to study and manipulate neuron activity, to decode molecular events at the single-cell level, and to analyze behavioral data. They pose exciting avenues to gain further insight into future sexual behavior research. Taken together, this work conveys the essential role of glutamate in sexual behavior.

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“…The progesterone receptor (PR: NCBI Gene ID:18667) is a member of the steroid receptor superfamily and plays essential roles in female reproductive events, such as the establishment and maintenance of pregnancy, menstrual cycle regulation, sexual behavior, and development of mammary glands. It is also responsible for developing the central nervous system by the regulation of cell proliferation and differentiation via a wide range of physiological process modulated by progesterone-mediated classical ligand-binding or non-classical novel non-genomic pathways (Garg et al, 2017;Leehy et al, 2018;Wu et al, 2018;Cenciarini and Proietti, 2019;González-Orozco and Camacho-Arroyo, 2019;Hawley and Mosura, 2019;Rudzinskas et al, 2019). In the clinic, steroidal PR agonists have been used in oral contraception and postmenopasusal hormone therapy (Fensome et al, 2005;Afhüppe et al, 2009;Lee et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

DeepSnap-Deep Learning Approach Predicts Progesterone Receptor Antagonist Activity With High Performance

Matsuzaka

Uesawa

2020

Front. Bioeng. Biotechnol.

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The progesterone receptor (PR) is important therapeutic target for many malignancies and endocrine disorders due to its role in controlling ovulation and pregnancy via the reproductive cycle. Therefore, the modulation of PR activity using its agonists and antagonists is receiving increasing interest as novel treatment strategy. However, clinical trials using the PR modulators have not yet been found conclusive evidences. Recently, increasing evidence from several fields shows that the classification of chemical compounds, including agonists and antagonists, can be done with recent improvements in deep learning (DL) using deep neural network. Therefore, we recently proposed a novel DL-based quantitative structure-activity relationship (QSAR) strategy using transfer learning to build prediction models for agonists and antagonists. By employing this novel approach, referred as DeepSnap-DL method, which uses images captured from 3-dimension (3D) chemical structure with multiple angles as input data into the DL classification, we constructed prediction models of the PR antagonists in this study. Here, the DeepSnap-DL method showed a high performance prediction of the PR antagonists by optimization of some parameters and image adjustment from 3Dstructures. Furthermore, comparison of the prediction models from this approach with conventional machine learnings (MLs) indicated the DeepSnap-DL method outperformed these MLs. Therefore, the models predicted by DeepSnap-DL would be powerful tool for not only QSAR field in predicting physiological and agonist/antagonist activities, toxicity, and molecular bindings; but also for identifying biological or pathological phenomena.

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Sex, Drugs, and the Medial Amygdala: A Model of Enhanced Sexual Motivation in the Female Rat

Cited by 11 publications

References 133 publications

Adolescent Social Isolation Reprograms the Medial Amygdala: Transcriptome and Sex Differences in Reward

Adolescent Social Isolation Reprograms the Medial Amygdala: Transcriptome and Sex Differences in Reward

Glutamate in Male and Female Sexual Behavior: Receptors, Transporters, and Steroid Independence

DeepSnap-Deep Learning Approach Predicts Progesterone Receptor Antagonist Activity With High Performance

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