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Protracted behavioral effects of neonatal morphine-pellet implantation in male rats
Insights
Early morphine exposure in male rats impairs long-term behaviors, including learning and stress response. This study highlights potential developmental neurotoxicity from neonatal opioid exposure.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Neonatal exposure to opioids can have lasting effects on development.
- Understanding the long-term consequences of early morphine exposure is crucial for public health.
Purpose of the Study:
- To investigate the long-term behavioral and physiological effects of early postnatal morphine exposure in male rats.
- To determine if the timing of morphine exposure influences these long-term outcomes.
Main Methods:
- Male rat pups received subcutaneous morphine, placebo, or no pellet implants on postnatal Day 5 or 11.
- Body weight, learning (Lashley III maze), activity wheel behavior, conditioned emotional response, and steroid response to morphine challenge were assessed at various time points.
- Reproductive success was evaluated by breeding treated males with females.
Main Results:
- Morphine-treated rats exhibited depressed body weights and impaired learning compared to controls.
- Early morphine exposure led to altered activity-wheel behavior and reduced suppression of conditioned emotional response.
- Protracted tolerance to morphine's pituitary-adrenal activating effects was observed in Day 5 exposed rats.
- No significant differences in reproductive parameters were found.
Conclusions:
- Early life morphine exposure in male rats results in persistent behavioral deficits and altered physiological responses.
- The timing of exposure appears to influence the specific long-term effects observed.
- These findings suggest potential developmental neurotoxicity associated with early opioid exposure.
Abstract:
Male rat pups (Charles Rivers CD albino strain) were implanted subcutaneously with a morphine (M), placebo (P), or no pellet (NP) on Day 5 or 11 of postnatal life. Body weights of both Day 5 and 11 drug-treated males were depressed below those of controls through Day 63 (p < 0.01). On Day 72, compared to P and NP controls, M-treated males showed impaired learning in a Lashley III maze. Day 5, but not Day 11 drug-treated animals showed greater activity-wheel behavior (p < 0.01) than controls on Days 85--86, and less suppression (p < 0.025) of a conditioned emotional response on Day 145. On Day 150, Day 5 M-treated animals showed a reduced steroid response (p < 0.05) to a challenge dose of M (18 mg/kg), suggesting protracted tolerance to the pituitary-adrenal activating effects of M. Members of each treatment group were successfully bred with females on Day 90; no group differences were found in litter size, sex ratios, or birth weights of the offspring. The results of this study indicate that early exposure to M causes long-term impairment of several behaviors in male rats.