The effect of nitric oxide on fentanyl and haloperidol-induced catalepsy in mice.
OBJECTIVE
This study was designed to investigate the role of nitric oxide on catalepsy induced by fentanyl and haloperidol.


METHODS
Male albino mice were treated either with fentanyl (0.1-0.2 mg kg-1, s.c.) or haloperidol (0.5-2 mg kg-1, i.p.). The non-selective nitric oxide synthase inhibitor, NG-nitro-L-arginine (10 mg kg-1, i.p.), selective neuronal nitric oxide synthase inhibitor, 7-nitroindazole (3 mg kg-1, i.p.), and nitric oxide donors, L-arginine (30-300 mg kg-1, i.p.) and D-arginine (30 mg kg-1, i.p.), were applied 20 min prior to fentanyl or haloperidol injection. A mu-opioid receptor antagonist naloxone (1 mg kg-1, i.p.) was also given in some groups. The cataleptic status of mice was assessed by placing animals in a rearing position in the cage. If the mouse maintained cataleptic posture for more than 20 s, it was scored as cataleptic and duration of catalepsy was expressed in terms of minutes.


RESULTS
Both NG-nitro-L-arginine and 7-nitroindazole prolonged fentanyl-induced catalepsy (fentanyl: 3.6+/-0.8 min; fentanyl+NG-nitro-L-arginine: 77.4+/-14.6 min, fentanyl+7-nitroindazole: 56.0+/-10.4 min; n=6; P<0.01). This effect was reversed by L-arginine and naloxone, but not by D-arginine. Nitric oxide synthase inhibitors also prolonged the cataleptic action of haloperidol but to a lesser extent (haloperidol: 72.0+/-6.3 min; haloperidol+NG-nitro-L-arginine: 98.5+/-6.3 min, haloperidol+7-nitroindazole: 89.6+/-2.2 min; n=6; P<0.05). The prolongation of haloperidol-induced catalepsy with nitric oxide synthase inhibitors was not reversed by L-arginine.


CONCLUSIONS
These results suggest a common mechanism between mu-opioid receptors and the nitric oxide system in the development of fentanyl-induced catalepsy in mice different from haloperidol-induced catalepsy.
Erkent
U
U
Hacettepe University, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey.
Iskit
A B
AB
Onur
R
R
Ilhan
M
M
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006220:Haloperidol; D005283:Fentanyl