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Perinatal treatment of rats with opiates affects the development of the blood-brain barrier transport system PTS-1
W A Banks1, A J Kastin, L M Harrison
1Veterans Affairs Medical Center-New Orleans, LA 70146, USA.
Insights
Neonatal morphine exposure enhances peptide transport system-1 (PTS-1) activity in adult rats. This blood-brain barrier system
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Neonatal morphine exposure impacts peptide transport system-1 (PTS-1) development.
- PTS-1 transports Tyr-MIF-1 and methionine enkephalin across the blood-brain barrier.
- PTS-1 activity correlates with brain methionine enkephalin levels.
Purpose of the Study:
- To investigate the long-term effects of perinatal morphine sulfate (MS) exposure on PTS-1 activity.
- To determine the influence of different opioid receptor agonists and antagonists on PTS-1 activity.
Main Methods:
- Rats received peripheral MS treatment during prenatal and neonatal periods.
- PTS-1 activity was assessed in adult rats.
- Comparative analysis with kappa and delta opioid agonists and antagonists.
Main Results:
- Perinatal MS treatment significantly enhanced PTS-1 activity in adult rats, increasing by 66% at 9 weeks.
- Morphine sulfate (mu agonist) was more potent than EKC (kappa) or pCl-DPDPE (delta) agonists.
- Methylnaltrexone blocked the MS-induced enhancement of PTS-1 activity.
Conclusions:
- Perinatal opioid exposure can permanently alter PTS-1 activity in the adult brain.
- Developmental opioid tone influences the maturation of blood-brain barrier transport systems.
- These findings highlight the lasting impact of early-life opioid exposure on neurodevelopment.
Abstract:
Previous results have shown that treatment of rats with morphine during the neonatal period can influence development of peptide transport system-1 (PTS-1), the blood-brain barrier transport system for Tyr-MIF-1 and methionine enkephalin. Previous work has suggested that the activity level of PTS-1 correlates with the concentration of methionine enkephalin in the brain. We show here that rats treated peripherally with morphine sulfate (MS) in both the prenatal and neonatal periods have enhanced activity of PTS-1. The degree of enhancement increases with age to reach a 66% increase in comparison with controls at age 9 weeks. The mu agonist MS was more powerful than the kappa agonist ethylketocyclazocine (EKC) or the delta agonist [D-Pen2.5,pCl-Phe4]enkephalin (pCl-DPDPE) in producing this effect. Opiate antagonists had complex effects with methylnaltrexone blocking the action of MS on PTS-1. These results show that the level of PTS-1 activity in adult rats can be modified by perinatal events that affect opiate tone during development.
