title: L-cycloserine: behavioural and biochemical effects after single and repeated administration to mice, rats and cats.
abstract: L-Cycloserine dose-dependently inhibited the activity of gamma-aminobutyric acid (GABA)-transaminase (GABA-T) and elevated the level of GABA in whole mouse brain with a peak effect 3-4 hr after a single intraperitoneal injection. At a dose (30 mg/kg) which elevated the level of GABA almost 4-fold, L-cycloserine moderately increased the content of alanine and slightly reduced that of aspartate, glutamate and glycine in the brain. L-Cycloserine (10-30 mg/kg, p.o. or i.p.) prevented tonic seizures induced by 3-mercaptopropionic acid (3-MPA) and audiogenic seizures in DBA/2 mice, without affecting those evoked by pentylenetetrazol, bicuculline and electroshock. Similarly small doses of L-cycloserine reduced the level of cGMP in the cerebellum of rats, prevented its elevation by 3-MPA and attenuated the hypothalamically-elicited rage reaction in cats. Larger doses of L-cycloserine (greater than 30-100 mg/kg) impaired the performance of mice in the rotarod, chimney and horizontal wire tests, and reduced spontaneous locomotor activity of rats. Upon repeated administration the inhibitory effect of L-cycloserine on the activity of GABA-T and on seizures elicited by 3-MPA in mice increased. In contrast, the depressant action of L-cycloserine on motor performance and locomotion declined in subchronically-treated mice and rats. The levels of amino acids in brain after repeated administration did not differ markedly from those in acutely-treated mice. It is suggested that small doses of L-cycloserine, probably by increasing GABAergic inhibition, reduce hyperexcitability in the brain in acute- and subchronically-treated animals. Larger doses of L-cycloserine, possibly by inducing multiple neurochemical changes, evoke central depressant effects which diminish during subchronic treatment.
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000927:Anticonvulsants; D001923:Brain Chemistry / Q000187:drug effects; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects*; D002531:Cerebellum / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D003523:Cycloserine / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011889:Rage / Q000187:drug effects; D051381:Rats; D012640:Seizures / Q000139:chemically induced
chemical_list: D000596:Amino Acids; D000927:Anticonvulsants; D003523:Cycloserine; D000612:4-Aminobutyrate Transaminase; D006152:Cyclic GMP