Effects of anticonvulsants and gamma-aminobutyric acid (GABA)-mimetic drugs on immunoreactive somatostatin and GABA contents in the rat brain.
Immunoreactive somatostatin (IR-SRIF) and gamma-aminobutyric acid (GABA) contents in the rat brain were investigated to study chronic effects of the treatment with anticonvulsants, carbamazepine (CBZ), valproic acid (VPA) and phenytoin (PHT). Decreased IR-SRIF levels were found in several brain regions after chronic treatment with VPA and CBZ. GABA concentrations were found to be increased significantly in chronic CBZ and VPA treatment in the rat brain, especially in limbic structures. PHT had no effect on both IR-SRIF and GABA contents in the rat brain. Effects of several GABA-mimetic drugs also were studied on IR-SRIF contents in the rat brain. Aminooxyacetic acid an inhibitor of GABA transaminase, induced a decrease in IR-SRIF concentration in the pyriform and entorhinal cortex, whereas ethanolamine-o-sulfate, another GABA-transaminase inhibitor and muscimol, a GABA receptor agonist had no effect on brain IR-SRIF after acute administration. The present results suggest that endogenous somatostatin has an important role for anticonvulsant properties of CBZ and VPA, but not of PHT. The relationship between the changes in IR-SRIF and the GABA transmitter system in the anticonvulsant action of CBZ and VPA remains to be clarified.
Nagaki
S
S
Division of Diagnostics, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Kato
N
N
Minatogawa
Y
Y
Higuchi
T
T
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology; D002850:Chromatography, Gel; D004347:Drug Interactions; D004983:Ethanolamines / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000032:analysis*; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000032:analysis* / Q000378:metabolism
D000927:Anticonvulsants; D004983:Ethanolamines; D000625:Aminooxyacetic Acid; D009118:Muscimol; D002220:Carbamazepine; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D010672:Phenytoin; C020619:ethanolamine O-sulfate