Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.13.39 (NO synthase)
 15,778 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. To determine whether nitric oxide (NO) was involved in tolerance and sensitization to the effects of phencyclidine (PCP), we examined NO synthase activity and the number of NADPH-diaphorase (NADPH-d)-positive cells in discrete brain regions of saline-, acute PCP- and repeated PCP-treated mice. We also investigated the effects of a NO synthase inhibitor, NG-nitro-L- arginine methyl ester (L-NAME), on the behavioural changes induced by repeated PCP treatment in mice. 2. Acute PCP (1, 3, and 10 mg kg-1, s.c.) treatment induced dose-dependent hyperlocomotion, motor incoordination and stereotyped behaviours, consisting of sniffing, head movement and ataxia in mice. 3. In mice treated repeatedly with PCP (1, 3, and 10 mg kg-1 day-1), s.c., once a day for 14 days), the sniffing, head movement, ataxia and motor incoordination induced by PCP were attenuated (indicating the development of tolerance to these behaviours), whereas the hyperlocomotion induced by PCP was potentiated (indicating the development of sensitization to hyperlocomotion). The development of tolerance and sensitization to PCP-induced behaviours in the repeated PCP-treated mice was more marked at the dose of 10 mg kg-1 day-1) than at other doses. 4. NO synthase activity in the cerebral cortex and cerebellum, but not in the striatum and hippocampus, was significantly decreased by acute PCP (10 mg kg-1) treatment in comparison with saline treatment, and such changes in activity in the cerebral cortex and cerebellum were reversed by repeated PCP treatment (10 mg kg-1 day-1). 5. The number of neurones containing NADPH-d reactivity in the cerebral cortex, nucleus accumbens, and striatum of acute and repeated PCP-treated mice showed no change in comparison with saline-treated mice. 6. Tolerance to PCP (10 mg kg-1 day-1)-induced ataxia and motor incoordination was significantly attenuated by combined treatment with L-NAME (50 mg kg-1 day-1 i.p.). 7. Sensitization to PCP-induced hyperlocomotion was further enhanced by combined treatment with L-NAME (50 mg kg-1 day-1). However, NG-nitro-D-arginine methyl ester (D-NAME, 50 mg kg-1 day-1, i.p.), a less active enantiomer of L-NAME, had no effect, suggesting a stereospecific mechanism. 8. The PCP-induced behaviours in animals that had exhibited tolerance and sensitization to PCP (10 mg kg-1 day-1) were not influenced by acute L-NAME (5 and 50 mg kg-1, i.p.) or D-NAME (50 mg kg-1, i.p.) treatment. 9. These results suggest that NO may play an important role in the development, but not in the maintenance, of tolerance and sensitization to the effect of PCP in mice.
 ...
PMID:Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice. 873 Jul 57

Previous studies have shown that nitric oxide (NO) is involved in the development of rapid tolerance to the motor incoordination produced by ethanol. In order to further investigate this involvement, three experiments were undertaken using the tilt-plane and the hypothermia tests. The first demonstrated that 7-nitroindazole (7-NI), a preferential neuronal NO synthase (nNOS) inhibitor, injected by intracerebroventricular (i.c.v.) route, blocked the development of rapid tolerance to ethanol-induced motor incoordination. This effect was prevented by i.c.v. injection of L-arginine. The second experiment showed that D-arginine did not influence the blockade of tolerance produced by 7-NI. The third experiment revealed that i.c.v. injection of 7-NI also blocked the development of tolerance to the hypothermic effect of ethanol. These results support the hypothesis that nNOS-derived NO participates in the development of rapid tolerance to ethanol.
 ...
PMID:Effects of intracerebroventricular administration of 7-nitroindazole on tolerance to ethanol. 1184 22