Abstract
Effects of nitric oxide synthase (NOS) inhibitors (l-N G-nitroarginine,l-N G-nitroarginine methyl ester) on precipitated opioid withdrawal were studied in morphine-dependent rats given naloxone, in order to assess the involvement of nitric oxide (NO) in opioid dependence.l-N G-Nitroarginine (7.5 mg/kg, IP, 1 h before naloxone or b.i.d. on days 4–7 of an 8-day morphine treatment) reduced wet dog shakes and weight loss; when given by osmotic pumps (15 mg/kg per day), the drug reduced wet dog shakes but not weight loss.l-N G-Nitroarginine methyl ester (60 mg/kg, 1 h before naloxone) also reduced wet dog shakes and weight loss. The results indicate that NOS inhibitors warrant further study as potential treatment of the opioid withdrawal syndrome.
This is a preview of subscription content, log in via an institution to check access.
References
Adams ML, Kalicki JM, Meyer ER, Cicero TJ (1993) Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor,N G-nitro-l-arginine methyl ester. Life Sci 52:PL245-PL249
Dwyer MA, Bredt DS, Snyder SH (1991) Nitric oxide synthase: irreversible inhibition byl-N G-nitroarginine in brainin vitro andin vivo. Biochem Biophys Res Commun 176:1136–1141
Garthwaite J (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. TINS 14:60–67
Gold MS, Redmond DE Jr, Kleber HD (1978) Clonidine blocks acute opiate-withdrawal symptoms. Lancet II(8080):599–602
Kimes AS, Bell JA, London ED (1990) Clonidine attenuates increased brain glucose metabolism during naloxone-precipitated morphine withdrawal. Neuroscience 34:633–644
Kolesnikov YA, Pick CG, Pasternak GW (1992)N G-Nitro-l-arginine prevents morphine tolerance. Eur J Pharmacol 221:399–400
Lambert LE, Whitten JP, Baron BM, Cheng HC, Doherty NS, McDonald IA (1991) Nitric oxide synthesis in the CNS endothelium and macrophages differs in its sensitivity to inhibition by arginine analogues. Life Sci 48:69–75
Rasmussen K, Fuller RW, Stockton ME, Perry KW, Swinford RM, Ornstein PL (1991a) NMDA receptor antagonists suppress behaviors but not norepinephrine turnover or locus coeruleus unit activity induced by opiate withdrawal. Eur J Pharmacol 197:9–16
Rasmussen K, Krystal JH, Aghajanian GK (1991b) Excitatory amino acids and morphine withdrawal: differential effects of central and peripheral kynurenic acid administration. Psychopharmacology 105:508–512
Rees DD, Palmer RM, Schulz R, Hodson HF, Moncada S (1990) Characterization of three inhibitors of endothelial nitric oxide synthasein vitro andin vivo. Br J Pharmacol 101:746–752
Trujillo KA, Akil H (1991) Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 251:85–87
Author information
Authors and Affiliations
Additional information
Abstracts were presented at meetings of the Society for Neuroscience in New Orleans, La., November 10–15, 1991 and of the American Society for Pharmacology and Experimental Therapeutics in Orlando, Fla., August 10–18, 1992
Rights and permissions
About this article
Cite this article
Kimes, A.S., Vaupel, D.B. & London, E.D. Attenuation of some signs of opioid withdrawal by inhibitors of nitric oxide synthase. Psychopharmacology 112, 521–524 (1993). https://doi.org/10.1007/BF02244904
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244904