Sex differences in morphine reward and glutamatergic regulation of the nucleus accumbens
2021-12
Loading...
View/Download File
Persistent link to this item
Statistics
View StatisticsJournal Title
Journal ISSN
Volume Title
Title
Sex differences in morphine reward and glutamatergic regulation of the nucleus accumbens
Authors
Published Date
2021-12
Publisher
Type
Thesis or Dissertation
Abstract
Opioid substance use disorder (SUD) affects millions of Americans, and death rates are increasing with the introduction of more potent opioids. Sex differences in the analgesic properties of opioids are well established. Whether similar sex differences are observed in the addictive properties of opioids is less-well understood. Making comparisons across experiments is problematic as methodology vary. In this dissertation, we examined the effects of morphine in male, female, gonadectomized (GDX) male, and GDX female mice using conditioned place preference, a behavioral paradigm specifically looking at the rewarding effects of a drug. We found that GDX males had significantly higher reinstatement to re-exposure to morphine compared to intact males, whereas there were no differences between intact males and intact females. Replacement of testosterone to GDX males did not cause their reinstatement to resemble that of intact males, suggesting that circulating testosterone was not the cause of the difference in behavior. In a separate study we next examined potential sex differences to acute morphine exposure using transgenic mice that allowed us to visualize neurons that were active during exposure to drug. Using Fos-TRAP, we quantified active neurons in the nucleus accumbens (NAc), a region known to be involved in processing of reward. With this acute exposure, we see that the NAc shell (NAcSh) has significantly more active cells after acute morphine than our control saline mice.
This importance of the NAcSh led us to finally examine excitatory inputs to the NAcSh and see how their activation impacts behavior in intra-cranial self-stimulation, specifically examining the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC). We find that female mice learn more quickly how to increase their time receiving mPFC stimulation compared to male mice. We also see that mPFC stimulation tends to cause animals to reside in the region where they receive stimulation, whereas vHPC stimulation causes animals to dart in and out of the stimulation region to increase stimulation time by bypassing the timeout period. Overall, these studies show us that, while there are no overt male / female differences in our CPP reward paradigm, we see male / GDX male differences that are not restored by addition of exogenous testosterone. We also showed that the NAcSh shows increased activation after acute morphine exposure, and that the two glutamatergic inputs we examined elicit differing strategies for increased stimulation of the region. Together, these findings show that further studying the sex differences in opioid reward and understanding how the NAcSh processes reward are important to help better treat SUD.
Keywords
Description
University of Minnesota Ph.D. dissertation. December 2021. Major: Neuroscience. Advisor: Paul Mermelstein. 1 computer file (PDF); ix, 112 pages.
Related to
Replaces
License
Collections
Series/Report Number
Funding information
Isbn identifier
Doi identifier
Previously Published Citation
Suggested citation
Lopresti, Natalie. (2021). Sex differences in morphine reward and glutamatergic regulation of the nucleus accumbens. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/226389.
Content distributed via the University Digital Conservancy may be subject to additional license and use restrictions applied by the depositor. By using these files, users agree to the Terms of Use. Materials in the UDC may contain content that is disturbing and/or harmful. For more information, please see our statement on harmful content in digital repositories.