Increased cortical nitric oxide release after phencyclidine administration.
Phencyclidine exerts psychotomimetic effects in humans and is used as a pharmacological animal model for schizophrenia. We, and others, have demonstrated that phencyclidine induces cognitive deficits in rats that are associated with schizophrenia. These cognitive deficits can be normalized by inhibition of nitric oxide synthase. The development of selective microelectrochemical nitric oxide sensors may provide direct evidence for the involvement of nitric oxide in these effects. The aim of the present study was to use LIVE (long term in vivo electrochemistry) to investigate the effect of phencyclidine, alone or in combination with the nitric oxide synthase inhibitor L-NAME, on nitric oxide levels in the medial prefrontal cortex of freely moving rats. Phencyclidine (2 mg kg(-1)) produced an increase in cortical nitric oxide levels and this increase was ameliorated by L-NAME (10 mg kg(-1)). Tentatively, the results from the present study provide a biochemical rationale for the involvement of nitric oxide in the phencyclidine model of schizophrenia.
Pålsson
Erik
E
Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden. erik.palsson@pharm.gu.se
Finnerty
Niall
N
Fejgin
Kim
K
Klamer
Daniel
D
Wass
Caroline
C
Svensson
Lennart
L
Lowry
John
J
D000704:Analysis of Variance; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D010622:Phencyclidine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D006213:Hallucinogens; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010622:Phencyclidine; D019331:NG-Nitroarginine Methyl Ester