Authors: ¹Rosado-Rodríguez, Fabiana Z., ²Richiez-Mateo, Wilma, ³Torres-Lloret, Mario E, ³Barreto-Estrada, Jennifer L.

Affiliations: ¹Department of Psychology, University of Puerto Rico, Río Piedras Campus, 00925-253, ²Department of Biology, University of Puerto Rico, Bayamón Campus, 00959; ³Department of Anatomy and Neurobiology, University of Puerto Rico-Medical Sciences Campus, San Juan, P.R., 00936.

Introduction: Opioid abuse disorder is one of the cognitive disorders that significantly affects the CNS, and its sustained use may lead to drug dependency despite harmful consequences. Over 75% of drug-related deaths in the year 2021 were associated with opioid use (CDC). The most recent opioid overdose death statistics (2020-2021) show that 29% of synthetic opioid-related overdose deaths were among men, while women accounted for 11% of the total figure (NIDA, 2023). Even with that difference, it has been observed that women more frequently use prescribed opioids in the United States, due to their higher likelihood of experiencing more pain. It has been shown that women have a greater dependence on this type of opioid, but they represent less than 30% of reported deaths. To understand the behavioral and neural basis of opioid addiction in males and females, we have established an animal model of addiction for the extinction of maladaptive behaviors. Previously, we demonstrated that male rats that extinguished drug-seeking behavior after undergoing both morphine-induced conditioned place preference (CPP), and extinction training, showed increased transcription of brain-derived neurotrophic factor (Bdnf) in the ventral striatum/nucleus accumbens (VS/NAc).

Results:  Increased BDNF protein expression was observed in the hippocampus (HPC) of males and females that extinguish morphine placed preference. Furthermore, females that did not receive extinction training (sham-extinction), showed a higher rate of extinction like behavior compared to males. Preliminary data show higher BDNF expression in the HPC of females that extinguish CPP in the absence of extinction training.

Methods: Therefore, with this project we seek to better characterize: 1) the percentage of female rats in the sham-extinction group that extinguished CPP according to the estrous cycle, 2) compare their withdrawal symptoms, and 3) determine BDNF expression. We hypothesize that females in the diestrus stage of the estrous cycle, where lower levels of estrogen are present, will be more likely to extinguish their morphine CPP.

Conclusion: Our study will contribute to determine whether the absence of extinction training is less effective for females when compared to males, and whether this is attributable to hormonal variations.

Support: Supported by: MBRS-SCORE-1SC2DA047809, NIGMS-RISE-R25GM061838 and NeuroID. IACUC Number: 9940112

Neuro ID Program Grant: 5R25NS080687.

Acknowledgments:

Neuro ID program

Grant: 5R25NS080687
Carmen S. Maldonado-Vlaar Ph.D.
Jose E. García- Arrarás Ph.D.
Marimar Velazquez Vargas
Natalia Figueroa Rosado

Principal Investigator: Dr. Jennifer L. Barreto-Estrada Ph.D

Grant NIH-SCORE-1SC2DA047809-02

NIH-NIGMS-R-16GM149491-01
Former graduate student: Mario Lloret-Torres

MBRS-RISE: R25GM061838

Personnel from the Animal Resources Center of the UPR-Medical Sciences Campus

Department of Biochemistry, INBRE PI: Dr. José Rodríguez Medina

Proteomics Center, Cancer Comprehensive Center, Dr. Loyda Meléndez

Keywords: BDNF, estrous cycle, CPP, morphine=extinction, addiction