MECHANISMS OF L-NG-NITRO ARGININE METHYL ESTER-INDUCED ANTINOCICEPTION IN MICE - A ROLE FOR SEROTONERGIC AND ADRENERGIC-NEURONS

1. The mechanisms involved in the antinociceptive action Of L-N-nitro arginine methyl ester (L-NAME) were investigated in mice. 2. Intraperitoneal administratiOn Of L-NAME produced a dose-dependent antinociception in the tail-flick, hot-plate and phenyl-p-quinone-induced writhing tests. 3. Pretreatment with the catecholamine depletors 6-hydroxydopamine(5 mug i.c.v.) or reserpine (5 mg/kg i.p.) or the serotonin synthesis inhibitor, p-chlorophenylalamine methyl ester (200 mg/kg i.p. on 2 consecutive days) resulted in a significant decrease in the antinociceptive effect of L-NAME. 4. Similarly, pretreatment with the selective alpha1-adrenoceptor antagonist prazonin (2.5 mg/kg, i.p.), or the non-selective alpha-adrenoceptor blocker, phentolamine (5 mg/kg, i.p.) antagonized the antinociceptive effect of L-NAME. 5. However, the administration of the selective alpha2-adrenoceptor antagonist, idazoxan (2.5 mg/kg i.p.) was without effect. 6. Likewise, pretreatment with the serotonin 5-HT2 receptor blocker, ketanserin (I mg/kg, i.p.), the D2 dopamine receptor antagonist ( +/- ) sulpiride (30 mg/kg, i.p.) or the opioid antagonist naloxone (5 mg/kg,i.p.) did not inhibit the antinociceptive effect Of L-NAME. 7. These results suggest that L-NAME produces antinociception in the mouse probably by an action on adrenergic and serotonergic synapses.