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

• Published in: Neurobiology of stress Vol. 17; p. 100431
• Main Authors: Dolgetta, Alexandra, Johnson, Megan, Fruitman, Kate, Siegel, Luke, Zhou, Yan, McEwen, Bruce S., Kreek, Mary Jeanne, Milner, Teresa A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2022; Elsevier
• Subjects: AMPA receptors; Drug associative-learning; Electron microscopy; from the Special Issue dedicated to Dr. Bruce McEwen; Edited by Matthew N. Hill, Richard Hunter and Lawrence Reagan; NMDA receptors; Pyramidal cells; ABC; CPP; DG; LTP; PFA; PARV; BSA; Oxy; SLM; NPY; NMDA; SO; SR; DAB; DOR; GluN1; ir; NMDA receptors; Electron microscopy; Drug associative-learning; CIS; ROI; SOM; MOR; PB; Pyramidal cells; GABA; AMPA receptors; GluA1; PM; SLu; Sal; TS; DOR, delta opioid receptor; DAB, diaminobenzidine; PM, plasma membrane; CPP, conditioned place preference; GABA, Gamma-amino butyric acid; GluA1, AMPA glutamate receptor subunit 1; TS, tris-buffered saline; DG, dentate gyrus; NPY, neuropeptide Y; Oxy, oxycodone; CIS, chronic immobilization stress; PARV, parvalbumin; SR, stratum radiatum; GluN1, NMDA, glutamate receptor subunit 1; SLu, stratum lucidum; SOM, somatostatin; BSA, bovine serum albumin; SO, stratum oriens; LTP, long-term potentiation; Sal, saline; NMDA, N-methyl-D-aspartate; PB, phosphate buffer; ir, immunoreactivity; ROI, region of interest; SLM, stratum lacunosum-moleculare; MOR, mu opioid receptor; ABC, avidin-biotin complex; PFA, paraformaldehyde
• DOI: 10.1016/j.ynstr.2022.100431
• ISSN: 2352-2895

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. •Baseline CA3 dendritic GluN1s are higher in Sal-females than Sal-males.•Oxy conditioned place preference (CPP) decreases CA3 dendritic GluN1s in females.•Chronic immobilization stress (CIS) increases CA3 dendritic GluN1 in Oxy-males.•CIS also increases CA3 dendritic GluA1 in Oxy-males.•CIS increases in GluN1 & GluA1 may increase glutamate sensitivity in males.