CIRCADIAN-RHYTHM-DEPENDENT EFFECTS OF L-N-G-NITROARGININE METHYL-ESTER (L-NAME) ON MORPHINE-INDUCED ANALGESIA

Circadian changes in the interactions between L-N-G-nitroarginine meth yl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, and morphi ne-induced antinociception were investigated by the mouse hot-plate te st. Both the basal pain sensitivity and morphine-induced analgesia und ergo significant 24h variations. L-NAME (40 mg/kg, ip) alone did not s how any antinociceptive activity, but potentiated morphine-induced ana lgesia when combined with morphine at all injection times. In terms of percentage absolute potentiation (%AP), L-NAME dramatically augmented the analgesic effect of morphine in the late dark period at 19 hours after lights on (HALO). It is concluded that nitric oxide (NO) is invo lved in the modulation of the analgesic effect of morphine; thus, the L-NAME and morphine combination might be beneficial in alleviating pai n.