Transgenerational Effects of Parental Morphine Withdrawal on Learning and Spatial Memory Processes and Hippocampal BDNF Protein Levels across Two Generations of Male Rats

Ataei, Saeid; Hosseini, Fatemeh; Seyyedi, Samaneh; Ranjbaran, Mina; Zarrindast, Mohammadreza; Ashabi, Ghorbangol

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Transgenerational Effects of Parental Morphine Withdrawal on Learning and Spatial Memory Processes and Hippocampal BDNF Protein Levels across Two Generations of Male Rats

, Mohammadreza Zarrindast

, Ghorbangol Ashabi ^*

Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran , gh-ashabi@tums.ac.ir

Abstract: (22 Views)

Introduction: The aim of this study was to investigate the effects of parental morphine withdrawal (maternal and paternal) on learning and spatial memory behaviors and hippocampal BDNF protein levels in first and second-generation offspring in a Wistar rat model. The focus of the research was on evaluating the behavioral and cognitive changes across two subsequent generations following parental exposure to morphine administration and withdrawal. Materials and Methods: Rats were divided into three groups: control, maternal morphine withdrawal group (MMW), and paternal morphine withdrawal group (PMW). Parental morphine dependence was induced using escalating oral doses (10 to 40 mg/kg for 3 weeks), followed by a 10-day withdrawal period to induce the morphine withdrawal phase. After confirming withdrawal symptoms, first and second generations were bred for behavioral assessments. Cognitive behavior of offspring was evaluated using the Barnes maze test. Afterward, rats were euthanized, and hippocampal brain tissue was extracted to measure hippocampal BDNF protein levels using an ELISA kit. Results: In the learning phase, initial delay times on days four and five showed a significant difference between the MMW group and control. Initial error counts on day five in the first generation differed significantly between the MMW and control groups. Moreover, initial error counts on day three in the first generation showed a significant difference between the PMW and control groups. In the second generation, initial error counts also showed a significant difference, but only on day three between the PMW and control groups. In the spatial memory test (day six), both MMW and PMW groups in the first generation exhibited greater delay times and error counts compared to controls. However, in the second generation, delay time and error count factors did not show a significant difference compared to controls. Furthermore, hippocampal BDNF protein levels in the first generation were significantly reduced in the morphine withdrawal offspring groups compared to the control group. Conclusion: The findings of this study indicate that parental morphine withdrawal results in significant behavioral and cognitive impairments in offspring. These results underscore the importance of monitoring and preventing morphine use in parents to reduce vulnerability in future generations.

Keywords: Substance Withdrawal Syndrome, Paternal Exposure, Maternal Exposure, Hippocampus

Type of Study: Research --- Open Access, CC-BY-NC | Subject: Cognitive Neuroscience

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