Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
Gene/Protein
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Query: EC:3.4.16.2 (
PCP
)
3,761
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The prefrontal cortex (PFC) is believed to play an important role in the cognitive impairments observed in schizophrenia and has also been shown to be involved in the modulation of prepulse inhibition (PPI), a measure of preattentive information processing that is impaired in schizophrenic individuals. Phencyclidine (
PCP
), a noncompetitive inhibitor of the NMDA receptor, exerts psychotomimetic effects in humans, disrupts PPI, and causes hypofrontality in rodents and monkeys. We have previously demonstrated that interfering with the production of nitric oxide (NO) can prevent a wide range of
PCP
-induced behavioral deficits, including PPI disruption. In the present study, the role of NO signaling for the behavioral and biochemical effects of
PCP
was further investigated. Dialysate from the medial PFC of mice receiving systemic treatment with
PCP
and/or the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg), was analyzed for cGMP content. Furthermore, a specific inhibitor of NO-sensitive
soluble guanylyl cyclase
(
sGC
), 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ, 0.01-1 mM), was administered into the medial PFC of mice in combination with systemic injections of
PCP
, followed by PPI and locomotor activity testing.
PCP
(5 mg/kg) caused an increase in prefrontal cGMP that could be attenuated by pretreatment with the NO synthase inhibitor, L-NAME. Moreover, bilateral microinjection of the
sGC
inhibitor, ODQ, into the medial PFC of mice attenuated the disruption of PPI, but not the hyperlocomotion, caused by
PCP
. The present study shows that NO/
sGC
/cGMP signaling pathway in the medial PFC is involved in specific behavioral effects of
PCP
that may have relevance for the disabling cognitive dysfunction found in patients with schizophrenia.
...
PMID:Nitric oxide signaling in the medial prefrontal cortex is involved in the biochemical and behavioral effects of phencyclidine. 1789 15
