On the role of endogenous GABA in the forced swimming test in rats.
GABA content was reduced in the nucleus accumbens, cortex and brainstem of rats after 5 but not after 45, 120 min or 24 hr, from the termination of the pretest session. This reduction was not observed in rats performing on rotarod. Intraperitoneal AOAA (25 mg/kg; 24, 5 and 1 hr before the test), reduced at the same extent immobility time regardless whether the animals had been exposed to a pretest session. In pretested animals, reduction in immobility time produced by AOAA (25 mg/kg X 3 times) was similar to that observed following 50 mg/kg, 5 hr before testing. This reduction was not antagonized by GABA antagonists bicuculline (2 mg/kg) or picrotoxin (2 mg/kg), given intraperitoneally 30 and 20 min before the test respectively. Intraperitoneal sodium valproate (200 or 400 mg/kg; 24, 5 and 1 hr before the test) and isoniazide (200 mg/kg) or 4-deoxypyridoxine (400 mg/kg), administered 1 or 1.5 hr before the test, were ineffective. AOAA (25 mg/kg X 3 times) gave a similar increase in GABA levels to 50 mg/kg only once in the brainstem, nucleus accumbens and hypothalamus and a greater increase in the other brain areas. After 5 hr from single dosing, 25 mg/kg AOAA increased GABA levels less than 50 mg/kg AOAA in the brainstem, nucleus accumbens, frontal cortex and striatum, and increased it to same extent in the other areas. Sodium valproate (400 mg/kg X 3 times) increased GABA levels in all brain areas, except hippocampus, although to a lesser extent than AOAA.
Borsini
F
F
A. Menarini S.a.S. Pharmaceuticals, Research Division, Firenze, Italy.
Mancinelli
A
A
D'Aranno
V
V
Evangelista
S
S
Meli
A
A
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003863:Depression / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D013550:Swimming; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000625:Aminooxyacetic Acid; D005680:gamma-Aminobutyric Acid