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Published on: December 14, 2014
Prenatal exposure to morphine impairs attention and impulsivity in adult rats
Elham Alaee1, Parisa Moazen1, Tommy Pattij2
1Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Insights
Prenatal morphine exposure in rats impairs cognitive functions, including learning and inhibitory control, persisting into adulthood. These effects on behavior were reversed by naloxone, suggesting opioid receptor involvement.
Area of Science:
- Neuroscience
- Developmental Psychology
- Pharmacology
Background:
- The opioid epidemic has led to increased prenatal morphine exposure in neonates.
- Long-term behavioral effects of prenatal opioid exposure are not well understood.
Purpose of the Study:
- To investigate the enduring effects of prenatal morphine exposure on cognitive functions in adult offspring.
- To evaluate the impact of morphine on learning, inhibitory control, and attention.
Main Methods:
- Pregnant rats were administered morphine or saline from embryonic days 11-18.
- Adult male offspring were tested in the 5-choice serial reaction time test (5-CSRTT).
- Cognitive performance was assessed under baseline conditions and after acute/subchronic morphine or naloxone challenges.
Main Results:
- Prenatal morphine exposure resulted in delayed learning and reduced inhibitory control in adult rats.
- Morphine challenges in prenatally exposed rats led to deficits in visuospatial attention.
- Naloxone administration abolished the observed behavioral deficits.
Conclusions:
- Prenatal morphine exposure has a causal effect on lifelong inhibitory control and learning.
- Adult morphine exposure exacerbates attention deficits in offspring with prenatal exposure.
- Opioid receptor antagonism with naloxone mitigates these behavioral impairments.
Rationale:
An alarming number of neonates born with prenatal exposure to morphine has resulted from the opioid epidemic; however, the long-term effects of prenatal opioid exposure on offspring behavior remain relatively unknown. In this study, we evaluated whether prenatal exposure to the mu opioid receptor agonist, morphine, has enduring effects on cognitive functions in adult life.
Methods:
On embryonic days 11-18 (E11-E18), female pregnant rats were injected subcutaneously with either morphine or saline twice daily. Adult male offspring that was prenatally exposed to saline or morphine was trained in the 5-choice serial reaction time test (5-CSRTT) to test their cognitive abilities under baseline conditions. Next, these rats were treated with saline (1 ml/kg), naloxone (1 mg/kg), and acute morphine (1, 3, 5 mg/kg), subcutaneously, once daily and following drug challenges rats were tested in the 5-CSRTT. Meanwhile, behavioral performance on training days between opioid drug challenges were analyzed to monitor possible drug-induced shifts in baseline performance. As a final experiment in order to investigate subchronic exposure to morphine, rats were injected with 5 mg/kg morphine for 5 days and then naloxone in the last day of the experiment (day 6).
Results:
Firstly, during acquisition of a stable baseline in the training phase, rats prenatally exposed to morphine showed delayed learning of the task demands. Furthermore, under baseline responding the rats prenatally exposed to morphine showed declined inhibitory control demonstrated by increased impulsive and compulsive-like responding compared to rats prenatally exposed to saline. Moreover, acute and subchronic morphine challenges in the rats prenatally exposed to morphine caused a deficit in visuospatial attention in comparison with saline treatment as well as the rats prenatally exposed to saline. These effects were abolished by naloxone.
Conclusion:
The current findings indicate a direct causal effect of prenatal morphine exposure on inhibitory control and task learning later in life, as well as deficits in attention following morphine exposure in adulthood.
