Repeated phencyclidine in monkeys results in loss of parvalbumin-containing axo-axonic projections in the prefrontal cortex.
BACKGROUND
Repeated exposure to the N-methyl-D-aspartate antagonist, phencyclidine, has been shown to result in biochemical and cognitive changes similar to aspects of schizophrenia. Recently, emerging evidence indicated that the symptoms of schizophrenia might result at least in part from dysfunction of local circuit neurons containing parvalbumin, including a loss of their axo-axonic projections to pyramidal neurons.


OBJECTIVE
In this report, we test if repeated exposure to phencyclidine in the primate shares this change to parvalbumin-containing cells and their axo-axonic structures.


METHODS
Eight adult male African green monkeys were treated with saline or phencyclidine (0.3 mg/kg BID x 14 days) and, after 8 days drug-free, perfused and fixed, and the principal sulcus was collected (Walker's area 46) for immunohistochemical analysis.


RESULTS
Prior treatment with phencyclidine resulted in a 40% reduction in the density of parvalbumin-containing axo-axonic structures. There was no apparent change in the lengths or laminar location of the axo-axonic projections. Additionally, there was no change in the total density or laminar location of parvalbumin-containing or calretinin-containing cell bodies in area 46.


CONCLUSIONS
These results indicate that repeated treatment with phencyclidine results in plastic changes in parvalbumin-containing local circuit neurons in the prefrontal cortex similar to that reported in schizophrenia and that these changes may contribute to the common cognitive disruption seen in both schizophrenic patients and the phencyclidine monkey model.
Morrow
Bret A
BA
Yale University School of Medicine, New Haven, CT 06511, USA. bret.morrow@yale.edu
Elsworth
John D
JD
Roth
Robert H
RH
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D064032:Calbindin 2; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010320:Parvalbumins / Q000187:drug effects* / Q000378:metabolism; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000648:ultrastructure; D064030:S100 Calcium Binding Protein G / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000503:physiopathology
D064032:Calbindin 2; D018691:Excitatory Amino Acid Antagonists; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D010622:Phencyclidine