Altered Dopamine Receptor and Dopamine Transporter Binding and Tyrosine Hydroxylase mRNA Expression Following Perinatal NMDA Receptor Blockade

• Published in: Neurochemical research Vol. 33; no. 7; pp. 1224 - 1231
• Main Authors: du Bois, Teresa Marie, Hsu, Ching-Wen, Li, Yulin, Tan, Yean Yeow, Deng, Chao, Huang, Xu-Feng
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.07.2008; Springer Nature B.V
• Subjects: Animals; Autoradiography; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain Chemistry - drug effects; Cell Biology; Cocaine - analogs & derivatives; Dopamine Antagonists; Dopamine Plasma Membrane Transport Proteins - drug effects; Dopamine Plasma Membrane Transport Proteins - metabolism; Dopamine Uptake Inhibitors; Excitatory Amino Acid Antagonists - pharmacology; Female; In Situ Hybridization; Neurochemistry; Neurology; Neurosciences; Original Paper; Phencyclidine - pharmacology; Pregnancy; Raclopride; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; RNA, Messenger - biosynthesis; Tyrosine 3-Monooxygenase - biosynthesis; Phencyclidine; NMDA receptor; Brain development; Dopaminergic system
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-007-9571-y

This study examined how perinatal phencyclidine (PCP) treatment would affect dopamine D 2 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. D 2 receptor and transporter binding was examined at four time-points (PN12, 18, 32 and 96) following injections. PCP treatment altered D 2 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.