Activation of medial prefrontal cortex neurons by phencyclidine is mediated via AMPA/kainate glutamate receptors in anesthetized rats.
Phencyclidine (PCP) is a psychotomimetic drug that elicits schizophrenia-like symptoms in healthy individuals, and animals administered PCP are now considered a reliable pharmacological model of schizophrenia. Recent studies have shown that systemically administered PCP produces long-lasting activation of medial prefrontal cortex (mPFC) neurons, and that hyperactivation of mPFC neurons plays a critically important role in the development of PCP-induced behavioral abnormalities. However, the receptors mediating this mPFC activation have not been clearly determined. Here, we examined the effects of local application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an AMPA/kainate glutamate receptor antagonist, scopolamine, a muscarinic acetylcholine receptor antagonist, and mecamylamine, a nicotinic acetylcholine receptor antagonist, on the increase in firing rate of mPFC neurons induced by systemic PCP in anesthetized rats. After tonic activation of mPFC neurons by PCP had been established, CNQX, scopolamine, or mecamylamine was iontophoretically applied or pressure-ejected on the recorded neuron. CNQX suppressed PCP-induced elevation of firing rate to baseline level, though scopolamine and mecamylamine each induced little change in firing rate. These findings suggest that PCP-induced activation of mPFC neurons is mediated primarily via AMPA/kainate glutamate receptors.
Katayama
T
T
Department of Neurophysiology, Fukushima Medical University School of Medicine, 1 Hikari-ga-oka, Fukushima 960-1295, Japan.
Jodo
E
E
Suzuki
Y
Y
Hoshino
K-Y
KY
Takeuchi
S
S
Kayama
Y
Y
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D000777:Anesthetics; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D018091:Receptors, AMPA; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D010622:Phencyclidine