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1- Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Abstract:
Introduction: Adolescence is a pivotal developmental stage characterized by increased susceptibility to opioid exposure, which can result in enduring modifications in pain sensitivity, emotional behavior, and stress regulation. This study examined the long-term effects of adolescent morphine exposure on nociception, anxiety- and depression-like behaviors, and plasma corticosterone levels in adulthood, employing a within-subject design to investigate behavioral and neuroendocrine correlations.
Methods: Adolescent rats were administered increasing doses of morphine (2.5–25 mg/kg, s.c.) twice daily from postnatal day (PND) 31 to 40. Following a 20-day drug-free washout period, behavioral assessments were conducted between PND 60 and 65. Anxiety-like behavior was evaluated using the open field and elevated zero maze tests, nociceptive sensitivity was assessed using the hargreaves and von-frey tests, and depression-like behavior was measured using the forced swimming test. Serum corticosterone levels were quantified 30 minutes after the forced swimming test. Principal component analysis (PCA) was also applied to standardized behavioral measures from morphine- and saline-treated animals to identify treatment-specific clustering and key behavioral contributors.
Results: Adolescent morphine exposure reduced anxiety-like behavior, pain sensitivity, and serum corticosterone levels, while increasing depression-like behavior in adulthood. Paw withdrawal latency was negatively correlated with open arm entries and time spent in the elevated zero maze, as well as immobility time in the forced swimming test. A positive correlation was observed between paw withdrawal latency and serum corticosterone levels. PCA of adult behavioral measures revealed distinct clustering of adolescent morphine- and saline-treated animals, indicating persistent treatment-specific behavioral profiles.
Conclusion: These findings suggest that adolescent morphine exposure induces long-lasting alterations in behavioral profile, including pain sensitivity, emotional behavior, and stress hormone regulation. The observed correlations between nociceptive thresholds, emotional behaviors, and corticosterone levels highlight the complex interplay between opioid exposure, affective states, and neuroendocrine function in adulthood.
Methods: Adolescent rats were administered increasing doses of morphine (2.5–25 mg/kg, s.c.) twice daily from postnatal day (PND) 31 to 40. Following a 20-day drug-free washout period, behavioral assessments were conducted between PND 60 and 65. Anxiety-like behavior was evaluated using the open field and elevated zero maze tests, nociceptive sensitivity was assessed using the hargreaves and von-frey tests, and depression-like behavior was measured using the forced swimming test. Serum corticosterone levels were quantified 30 minutes after the forced swimming test. Principal component analysis (PCA) was also applied to standardized behavioral measures from morphine- and saline-treated animals to identify treatment-specific clustering and key behavioral contributors.
Results: Adolescent morphine exposure reduced anxiety-like behavior, pain sensitivity, and serum corticosterone levels, while increasing depression-like behavior in adulthood. Paw withdrawal latency was negatively correlated with open arm entries and time spent in the elevated zero maze, as well as immobility time in the forced swimming test. A positive correlation was observed between paw withdrawal latency and serum corticosterone levels. PCA of adult behavioral measures revealed distinct clustering of adolescent morphine- and saline-treated animals, indicating persistent treatment-specific behavioral profiles.
Conclusion: These findings suggest that adolescent morphine exposure induces long-lasting alterations in behavioral profile, including pain sensitivity, emotional behavior, and stress hormone regulation. The observed correlations between nociceptive thresholds, emotional behaviors, and corticosterone levels highlight the complex interplay between opioid exposure, affective states, and neuroendocrine function in adulthood.
Keywords: adolescent morphine exposure, emotional behaviors, pain sensitivity, corticosterone, behavioral and neuroendocrine correlations
Type of Study: Original |
Subject:
Behavioral Neuroscience
Received: 2025/07/29 | Accepted: 2025/09/20
Received: 2025/07/29 | Accepted: 2025/09/20
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