Sex and chronic stress alter the distribution of glutamate receptors within rat hippocampal CA3 pyramidal cells following oxycodone conditioned place preference.

TitleSex and chronic stress alter the distribution of glutamate receptors within rat hippocampal CA3 pyramidal cells following oxycodone conditioned place preference.
Publication TypeJournal Article
Year of Publication2022
AuthorsDolgetta A, Johnson M, Fruitman K, Siegel L, Zhou Y, McEwen BS, Kreek MJeanne, Milner TA
JournalNeurobiol Stress
Volume17
Pagination100431
Date Published2022 Mar
ISSN2352-2895
Abstract

Glutamate receptors have a key role in the neurobiology of opioid addiction. Using electron microscopic immunocytochemical methods, this project elucidates how sex and chronic immobilization stress (CIS) impact the redistribution of GluN1 and GluA1 within rat hippocampal CA3 pyramidal cells following oxycodone (Oxy) conditioned place preference (CPP). Four groups of female and male Sprague-Dawley rats subjected to CPP were used: Saline- (Sal) and Oxy-injected (3 mg/kg, I.P.) naïve rats; and Sal- and Oxy-injected CIS rats. GluN1: In both naive and CIS rats, Sal-females compared to Sal-males had elevated cytoplasmic and total dendritic GluN1. Following Oxy CPP, near plasmalemmal, cytoplasmic, and total GluN1 decreased in CA3 dendrites of unstressed females suggesting reduced pools of GluN1 available for ligand binding. Following CIS, Oxy-males (which did not acquire CPP) had increased GluN1 in all compartments of dendrites and spines of CA3 neurons. GluA1: There were no differences in the distribution GluA1 in any cellular compartments of CA3 dendrites in naïve females and males following either Sal or Oxy CPP. CIS alone increased the percent of GluA1 in CA3 dendritic spines in males compared to females. CIS Oxy-males compared to CIS Sal-males had an increase in cytoplasmic and total dendritic GluA1. Thus, in CIS Oxy-males increased pools of GluN1 and GluA1 are available for ligand binding in CA3 neurons. Together with our prior experiments, these changes in GluN1 and GluA1 following CIS in males may contribute to an increased sensitivity of CA3 neurons to glutamate excitation and a reduced capacity to acquire Oxy CPP.

DOI10.1016/j.ynstr.2022.100431
Alternate JournalNeurobiol Stress
PubMed ID35535260
PubMed Central IDPMC9076964