Age-dependent changes in brain glycine concentration and strychnine-induced seizures in the rat.
Glycine levels and receptor binding were measured in the medulla and spinal cord of 2-month, 10-month, and 24-month-old Fischer 344 rats. The behavioral response to the administration of the glycine antagonist, strychnine, was also evaluated in 2- and 24-month-old animals to investigate the relevance of these parameters to the susceptibility to seizures. Significant reductions in glycine in both the spinal cord and medulla occurred from 2 to 24 months of age. The glycine precursors, serine and threonine, were decreased only in the spinal cord. [3H]Strychnine binding was also decreased by 38% and 34% in the medulla and spinal cord, respectively, of 24-month-old rats compared to 2-month-olds. [3H]GABA binding was similarly reduced while no age-related changes in [3H]diazepam binding in the spinal cord were detected. Comparison of 2- and 24-month-old animals after systemic injection of 1.75 mg/kg strychnine showed that senescent animals have a higher incidence of seizures and mortality compared to young animals. Decreases in glycinergic neurotransmission may lower strychnine seizure threshold in the aged animal.
Hunter
C
C
Graduate Program in Biomedical Sciences, Mount Sinai School of Medicine, New York, NY 10029.
Chung
E
E
Van Woert
M H
MH
D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D005998:Glycine / Q000378:metabolism*; D008526:Medulla Oblongata / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D013331:Strychnine / Q000378:metabolism* / Q000494:pharmacology
D013331:Strychnine; D005998:Glycine