Excitatory and inhibitory neurotransmission is chronically altered following perinatal NMDA receptor blockade.
N-methyl-D-aspartate (NMDA) receptor blockade in rodents induces behavioural and neurochemical changes reminiscent of schizophrenia symptoms and pathology. To examine how NMDA receptor blockade affects glutamatergic and GABAergic pathways when administered during early brain development, [3H]MK-801 and [3H]muscimol binding to NMDA and GABA(A) receptors was examined at four time-points following injections of phencyclidine (PCP) or saline on postnatal days (PN)7, 9 and 11. [3H]MK-801 binding was significantly increased in PCP-treated rats in the thalamus from PN18 to PN96, in the prefrontal and anterior cingulate cortices at PN32, and in the hippocampus at PN96. In a similar manner, [3H]muscimol binding was increased in PCP-treated rats in the thalamus and hippocampus from PN18 to PN96, and in the prefrontal and anterior cingulate cortices at PN32. Glutamatergic and GABAergic transmission is therefore chronically altered by this treatment, which has relevance to disease processes that may be involved in schizophrenia.
du Bois
Teresa Marie
TM
Schizophrenia Research Institute (SRI), Sydney, Australia.
Deng
Chao
C
Han
Mei
M
Newell
Kelly Anne
KA
Huang
Xu-Feng
XF
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development; D001931:Brain Mapping; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D011247:Pregnancy; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D016291:Dizocilpine Maleate; D010622:Phencyclidine