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Updated: Jul 7, 2026
Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
Published on: August 10, 2012
Altered dopamine receptor and dopamine transporter binding and tyrosine hydroxylase mRNA expression following
Teresa Marie du Bois1, Ching-Wen Hsu, Yulin Li
1Schizophrenia Research Institute (SRI), Sydney, Australia.
Insights
Early exposure to phencyclidine (PCP) significantly alters dopamine D2 receptor binding and dopamine transporter (DAT) levels in developing rats. These changes persist into adulthood, indicating long-term effects on the dopaminergic system.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Pharmacology
Background:
- Perinatal exposure to drugs like phencyclidine (PCP) can disrupt neurodevelopment.
- The dopaminergic system plays a crucial role in various brain functions and is sensitive to early-life insults.
- Understanding long-term neurochemical changes is vital for assessing developmental risks.
Purpose of the Study:
- To investigate the long-term effects of perinatal phencyclidine (PCP) exposure on dopamine D2 receptor and dopamine transporter (DAT) binding.
- To examine these neurochemical alterations at different developmental stages following PCP treatment cessation.
- To assess potential long-term changes in dopamine system function.
Main Methods:
- Female rat pups were treated with PCP or saline on postnatal days 7, 9, and 11.
- Dopamine D2 receptor and DAT binding were measured at postnatal days 12, 18, 32, and 96.
- Tyrosine hydroxylase mRNA expression was analyzed in adult rats.
Main Results:
- PCP treatment led to decreased dopamine D2 receptor binding (22-33%) in adulthood in the nucleus accumbens and caudate putamen.
- A significant increase in DAT binding was observed in the caudate putamen of adult rats.
- Tyrosine hydroxylase mRNA expression was elevated by 25% in the ventral tegmental area of adult rats.
Conclusions:
- Perinatal PCP exposure induces lasting alterations in the brain's dopaminergic system.
- These findings suggest that early NMDA receptor hypofunction can lead to persistent changes in dopamine receptor and transporter levels.
- The observed alterations may indicate a long-term increase in dopamine output, impacting brain function development.
Abstract:
This study examined how perinatal phencyclidine (PCP) treatment would affect dopamine D2 receptor and dopamine transporter (DAT) binding at different stages after treatment cessation. Female rat pups received injections of PCP (10 mg/kg, s.c.) or saline on postnatal day (PN)7, 9 and 11. D2 receptor and transporter binding was examined at four time-points (PN12, 18, 32 and 96) following injections. PCP treatment altered D2 receptor binding throughout development, with a final end-point of 22-33% decreased binding at adulthood in the nucleus accumbens and caudate putamen (P < 0.01), accompanied by a small but significant increase in DAT binding in the caudate putamen. Tyrosine hydroxylase mRNA expression was also significantly increased by 25% (P < 0.05) in the ventral tegmental area of adult rats, suggesting that this model may produce a long-term increase in dopamine output. This study demonstrates that early insult to the brain from NMDA receptor hypofunction alters the dopaminergic system at different stages of development.
