Phencyclidine interferes with the hippocampal gating of nucleus accumbens neuronal activity in vivo.
The N-methyl-D-aspartate channel blocker phencyclidine is known to induce psychotic episodes in normal subjects and exacerbate psychosis in schizophrenics; however, its site of action is not clear. The prefrontal cortex, hippocampus, and basal ganglia are brain regions that appear to play a role in the pathophysiology of schizophrenia, and therefore are the most likely to be involved in the psychotomimetic action of phencyclidine. In this study, systemic administration of phencyclidine reduced the frequency and duration of the spontaneously occurring depolarized plateaus observed in the membrane potential of accumbens neurons recorded intracellularly in vivo. Furthermore, recordings from rats pretreated with phencyclidine yielded proportionately fewer neurons showing depolarized events compared with untreated animals. These results suggest that phencyclidine may interfere with the generation of the depolarized ("up") state of the accumbens neuron membrane potential, which we had previously shown is dependent upon hippocampal input and is necessary for action potential discharge in these neurons. This action of phencyclidine is proposed to impair the flow of cortical information through the nucleus accumbens, and thereby mimic the consequences of the hippocampal deficit proposed to contribute to the pathophysiology of schizophrenia.
O'Donnell
P
P
Department of Neuroscience, University of Pittsburgh, PA 15260, USA.
Grace
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D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D010622:Phencyclidine