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Glutamate Receptor Antagonists Block Estradiol Induced Generalization

  1. Open Access Kent State
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  4. 2016 - Kent State University Undergraduate Symposium on Research, Scholarship and Creative Activity
  5. Kent State University Undergraduate Symposium on Research, Scholarship and Creative Activity
  6. Glutamate Receptor Antagonists Block Estradiol Induced Generalization
Author(s)
  • Jordan M Adkins
  • Michael S Gray
  • Megan J Butler
  • Haley L Courtney
  • Joseph Lynch
  • Aaron M. Jasnow
Abstract

In general, women are more susceptible than males to anxiety disorders, which are commonly characterized by fear generalization; the inability to discriminate an aversive and neutral stimulus. Work in our lab demonstrates that female rats generalize contextual fear at a faster rate compared with males; a process driven by estradiol. We then sought to find out the mechanisms by which estradiol induces generalization. Related work suggests estradiol can influence structural changes within certain brain regions by increasing the amount of glutamatergic receptors, which promote learning and memory. Given this, we hypothesized that estradiol induced generalization was a result of enhanced glutamatergic signaling. To assess this, ovarectomized rats were trained in a passive avoidance paradigm in context A, and injected with estradiol or vehicle 24 hours later. Twenty-four hours post-injection, animals received infusions of an NMDA antagonist (APV), AMPA antagonist (NBQX), or vehicle. Infusions occurred in either the dorsal CA1 of the hippocampus or the anterior cingulate cortex—regions that play a role in time-dependent context fear generalization. When tested, both glutamate receptor antagonists attenuated estradiol induced generalization in the CA1 and ACC, but had no effect on fear generalization when administered alone, indicating that glutamatergic signaling is essential for estradiol induced generalization. Follow up experiments will identify the subunit-specific NMDA and AMPA receptor needed for estradiol induced generalization. Identifying the mechanisms underlying estradiol’s influence on fear generalization will allow researchers to better understand the sex differences seen in anxiety disorders, and could lead to improved treatments for these disorders.

Format
Conference Proceeding
Publication Date
2016-03-15
Contributor(s)
Faculty Mentor
Dr. Aaron Jasnow
Subject
  • Biological Psychology
Modified Abstract

Work in our lab demonstrates that female rats generalize contextual fear faster than males; a process driven by estradiol. We hypothesized that estradiol induced generalization was a result of enhanced glutamatergic signaling. To assess this, ovarectomized rats were trained in passive avoidance and injected with estradiol or vehicle 24 hours later. Twenty-four hours post-injection, animals received infusions of an NMDA antagonist (APV), AMPA antagonist (NBQX), or vehicle into the dorsal CA1 or the anterior cingulate cortex. When tested both glutamate receptor antagonists attenuated estradiol induced generalization, but had no effect when administered alone, indicating that glutamatergic signaling is essential for estradiol induced generalization. Identifying the mechanisms underlying estradiol’s influence on fear generalization will allow researchers to better understand the sex differences seen in anxiety disorders.

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