Effects of NG-nitro-L-arginine methyl ester, 7-nitro indazole, and agmatine on pentylenetetrazol-induced discriminative stimulus in Long-Evans rats

This study was undertaken to determine any role that nitric oxide (NO) may play in the discriminative stimuli produced by pentylenetetrazol (PTZ). The PTZ-induced discriminative stimulus is pharmacologically similar to anxiety in humans and is used in a behavioral assay of anxiety (the PTZ model of anxiety). In the present study, effects of L-N(G)-nitro arginine methyl ester (L-NAME), 7-nitroindazole (7-NI) and agmatine, NO synthase (NOS) inhibitors, on PTZ-induced discriminative stimulus were investigated in male Long-Evans rats (330-350 g). Rats were trained to discriminate PTZ (16 mg/kg) from saline using a two-lever, food-reinforced choice procedure (FR 10). The rats that met the training criteria were injected with L-NAME (15, 30, and 60 mg/kg), 7-NI (15 and 30 mg/kg), agmatine (20, 40, and 60 mg/kg), and saline or vehicle intraperitoneally before each test. They were tested for the PTZ-discrimination to determine if the NOS inhibitors produce discriminative stimulus similar to PTZ or if they block PTZ-induced discrimination. Treatment with the NOS inhibitory drugs neither substituted for PTZ nor altered the PTZ lever selection in any other way. These findings suggest that PTZ-induced discriminative stimulus may not be related to NO-mediated central mechanisms.