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The effect of nitric oxide on fentanyl and haloperidol-induced catalepsy in mice

Published online by Cambridge University Press:  01 March 2006

U. Erkent ,
A. B. Iskit ,
R. Onur  and
M. Ilhan
U. Erkent
Affiliation:
Hacettepe University, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey
A. B. Iskit
Affiliation:
Hacettepe University, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey
R. Onur
Affiliation:
Hacettepe University, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey
M. Ilhan
Affiliation:
Hacettepe University, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey
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Summary

Background and objectives: 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 μ-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. Conclusion: These results suggest a common mechanism between μ-opioid receptors and the nitric oxide system in the development of fentanyl-induced catalepsy in mice different from haloperidol-induced catalepsy.

Keywords

FENTANYL, HALOPERIDOL, NITRIC OXIDE OPIOID, DOPAMINE, CATALEPSY
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 23 , Issue 7 , July 2006 , pp. 580 - 585
Copyright
© 2006 European Society of Anaesthesiology

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Footnotes

Preliminary account of the present data was presented in abstract form at the XVII. Biannual Meeting of the Turkish Pharmacological Society in October, 2003, Belek-Antalya.

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