Altered dopamine receptor and dopamine transporter binding and tyrosine hydroxylase mRNA expression following perinatal NMDA receptor blockade.
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.
du Bois
Teresa Marie
TM
Schizophrenia Research Institute (SRI), Sydney, Australia.
Hsu
Ching-Wen
CW
Li
Yulin
Y
Tan
Yean Yeow
YY
Deng
Chao
C
Huang
Xu-Feng
XF
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects; D003042:Cocaine / Q000031:analogs & derivatives; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D017403:In Situ Hybridization; D010622:Phencyclidine / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis*; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D020891:Raclopride; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D010622:Phencyclidine