Sex differences in synaptic plasticity within the reward system: the role of PKMζ and implications for opioid use disorder

Despite the fact that more men are diagnosed with substance use disorder, women escalate their drug consumption faster, exhibit higher craving during withdrawal, and have poorer treatment outcomes. Furthermore, as our cultural expectations of men and women have changed, there has been an increase in drug use in women and this increase is likely to persist. Preclinically, female rodents show stronger behavioral responses to drugs of abuse during initiation, escalation, and reinstatement of drug seeking. These behavioral differences are accompanied by alterations in structural plasticity within the mesocorticolimbic reward system. However, little is known about what functional sex differences exist in glutamate transmission in these circuits. The goal of these experiments was to determine functional sex differences in reward circuitry that may underlie behavioral sex differences in substance use disorder. We found heightened glutamate transmission in both the medial prefrontal cortex and nucleus accumbens in females compared to males. These findings corresponded with the nucleus accumbens being less plastic in females. We then investigated the role of PKMζ, a glutamatergic AMPA receptor trafficking protein, in plasticity and opioid-taking. We found PKMζ plays a role in synaptic plasticity within the nucleus accumbens and it works to blunt oxycodone-taking and motivation in a dose-dependent manner. Taken together these findings suggest there are functional sex differences at many levels within the reward system and gaining a better understanding of these differences could provide insight into improved treatments for substance use disorder.

Grantor dc:publisher

Temple University. Libraries

Year dc:date.issued

2023

Author dc:creator

• Knouse, Melissa

Advisor dc:contributor.advisor

• Briand, Lisa A.

Committee members dc:contributor.committeemember

• Wimmer, Mathieu
• Parikh, Vinay
• Sutton Hickey, Ames
• Bangasser, Debra A.
• Kirby, Lynn

• Psychology
• Neurosciences
• AMPA
• Glutamate
• Nucleus accumbens
• PKMζ
• Substance use disorder
• Synaptic plasticity

Statement dc:rights

• IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/20.500.12613/8600

OAI identifier oai:identifier

oai:scholarshare.temple.edu:20.500.12613/8600