Related Experiment Videos
Effect of prenatal exposure to phencyclidine on the postnatal development of the cholinergic system in the rat
1Department of Pharmacology and Mental Retardation Research Center, University of California, Los Angeles.
Insights
Prenatal exposure to phencyclidine (PCP) did not lead to tolerance in rat pups. These pups remained sensitive to a challenge dose of PCP, indicating altered neurodevelopment.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Pharmacology
Background:
- Prenatal exposure to drugs of abuse can impact neurodevelopment.
- Phencyclidine (PCP) is an NMDA receptor antagonist with known psychotomimetic effects.
- The cholinergic system plays a critical role in cognitive functions and is a potential target for developmental disruptions.
Purpose of the Study:
- To investigate the long-term effects of prenatal phencyclidine (PCP) exposure on the postnatal development of the cholinergic system.
- To determine if prolonged prenatal PCP exposure induces tolerance to its effects on acetylcholine and choline levels.
- To assess the sensitivity of offspring to a challenge dose of PCP at different postnatal ages.
Main Methods:
- Pregnant rats were administered daily doses of PCP throughout gestation.
- Offspring were challenged with PCP on postnatal days 21 and 35.
- Levels of acetylcholine and choline, and choline incorporation into acetylcholine, were measured in the frontal cortex and neostriatum.
Main Results:
- Rat pups prenatally exposed to PCP exhibited increased sensitivity to a challenge dose of PCP at postnatal day 21.
- This heightened sensitivity persisted, indicating a lack of tolerance development.
- Alterations in cholinergic system parameters were observed in response to prenatal PCP exposure.
Conclusions:
- Prenatal PCP exposure significantly impacts the developing cholinergic system.
- Prolonged prenatal exposure to PCP does not result in tolerance to its acute effects.
- These findings suggest potential long-lasting neurodevelopmental consequences of in utero PCP exposure.
Abstract:
The purpose of this study was to examine the effect of prenatal exposure to phencyclidine (PCP) on the postnatal development of the cholinergic system in the neostriatum and the neocortex. Pregnant females were injected daily with PCP (0.5 mg/kg s.c.) from conception to parturition. On postnatal day 21 or 35, pups were injected with a challenge dose of PCP (0.5 mg/kg s.c.). The levels of acetylcholine and choline were measured, as well as the incorporation of deuterium-labelled choline into newly synthesized acetylcholine in the frontal cortex and neostriatum. The data demonstrate that even at 21 days, rat pups exposed to PCP in utero were more sensitive to a challenge dose of PCP than the saline controls. Thus, a tolerance to PCP, even after a prolonged prenatal exposure did not develop.