[Toxicity of AMPA, an excitatory amino acid, to rat spinal cord neurons under intrathecal administration].
The neurotoxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), an agonist for glutamate receptors, was investigated by infusing adult rats with this agent intrathecally for either a short term (2 hours) or a long term (7 days) using a mechanical pump or a mini-osmotic pump, respectively. In the short-term infusion group, spasticity of the hindlimbs developed during infusion at 0.5 nmol/h or more of AMPA, tremors at 50 nmol/h or more, and flaccidity at 65 nmol/h or more. One day later, flaccid paralysis of the hindlimbs and urinary incontinence were observed in the rats that received 50 nmol/h (total dose: 100 nmol) or more of AMPA. These symptoms were thought to be permanent. On the other hand, in the long-term infusion group, behavioral changes were apparent only after second postoperative day, when rats displayed hindlimb palsy or urinary incontinence. Behavioral deficits became progressively severe, and rats usually displayed both hindlimb paraplegia and urinary incontinence by the 7th postoperative day. These progressive behavioral deficits were induced in a dose-dependent manner in rats that received AMPA at doses greater than 0.1 nmol/h. Gliosis with neuronal loss involving the partial (lumbar segments) and whole (sacral segments) gray matter of the spinal cord was induced in rats that received AMPA at doses greater than 50 nmol/h in the short-term infusion group and greater than 0.1 nmol/h in the long-term infusion group.(ABSTRACT TRUNCATED AT 250 WORDS)
Nakamura
R
R
Third Department of Internal Medicine, National Defense Medical College.
Kamakura
K
K
Kwak
S
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D014549:Urinary Incontinence / Q000139:chemically induced; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage / Q000633:toxicity*
D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid