Inhibition of sacral parasympathetic preganglionic neurons by GABA, glycine, 5-hydroxtryptamine and norepinephrine

Sacral parasympathetic preganglionic discharges recorded from the pelvic nerve were evoked by stimulation of sacral afferent fibers, descending pathways in the dorsolateral spinal cord, or medullary vesico-constrictor centers. Evoked activity was summed and integrated with a signal averaging computer in 67 spinal or decerebrate cats. Coadministration of picrotoxin (2 mg/kg) and strychnine (.02 mg/kg), but neither alone, increased evoked activity by 4 to 10 times. In addition, after treatment with both picrotoxin and strychnine the increases in bladder pressures evoked by stimulus trains were enhanced by 2-12 times. Bicuculline (0.5 mg/kg) could be substituted for picrotoxin. Similar increases in evoked pelvic nerve activity were induced by strychnine (0.1 mg/kg) in cats depleted of GABA stores with semicarbazide (200 mg/kg). D,L-5-HTP (50 mg/kg) depressed evoked activity in both normal and convulsant-treated cats. Depression by 5-HYP or L-dopa was augmented by chlorimipramine or protriptyline, respectively. These results indicate that sacral parasympathetic preganglionic neurons are under strong, local tonic inhibition mediated by both GABA and glycine. The 5-HT and NE bulbospinal neurons that terminate in the intermediolateral portion of the sacral spinal cord also appear to exert an inhibitory influence. The results are compatible with clinical experience in patients with loss of bladder function due to lesions of the spinal cord.