Effect of repeated treatment with a gamma-aminobutyric acid receptor agonist on postnatal neural development in rats.
The effect of treatment with the gamma-aminobutyric acid (GABA) agonist tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) on neural development was monitored in rats by following the expression of the neuron-specific proteins neural cell adhesion molecule (NCAM), D1, and D3 as well as the enzymes glutamate decarboxylase (GAD) and glutamate dehydrogenase (GLDH). As judged from the effect of the treatment on the expression of NCAM and GAD, GABA agonists have the capacity to accelerate and enhance neuronal development during the early postnatal period. However, as judged from the expression of D1- and D3-protein some adverse late effects may result from prolonged treatment with high doses of GABA agonists. The decrease in GLDH specific activity observed in THIP-treated rats during their late postnatal development possibly indicates a repression of glutamatergic neurons.
Meier
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E
Department of Biochemistry A, Panum Institute, Copenhagen, Denmark.
Jørgensen
O S
OS
Schousboe
A
A
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007555:Isoxazoles; D009419:Nerve Tissue Proteins; D010080:Oxazoles; C028116:nervous system specific protein D1; C028117:nervous tissue specific protein D3; D005680:gamma-Aminobutyric Acid; D005969:Glutamate Dehydrogenase; D005968:Glutamate Decarboxylase; C015542:gaboxadol