Attenuation of some signs of opioid withdrawal by inhibitors of nitric oxide synthase.

Effects of nitric oxide synthase (NOS) inhibitors (L-NG-nitroarginine, L-NG-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-NG-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-NG-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 treatments of the opioid withdrawal syndrome.