TY - JOUR
T1 - Long-term effects of excitatory amino acid antagonists NBQX and MK-801 on the developing brain
AU - Tandon, Pushpa
AU - Liu, Zhao
AU - Stafstrom, Carl E.
AU - Sarkisian, Matthew
AU - Werner, Suzanne J.
AU - Mikati, Mohamad
AU - Yang, Yili
AU - Holmes, Gregory L.
N1 - Funding Information:
Supported by grants from the NINDS (NS27984), the Stephen Linn Fund, and the March of Dimes Birth Defects Foundation to G.L.H. and C.E.S.
PY - 1996/9/2
Y1 - 1996/9/2
N2 - Because of the critical role of excitatory amino acids (EAAs) in epileptogenesis and seizure-induced brain damage, EAA antagonists are now being considered as a possible therapy for seizures. However, during development EAAs play a pivotal role in learning, memory, and brain plasticity. To evaluate the long-term effects of a short course of EAA antagonists on the developing brain, a non-NMDA antagonist, NBQX, or a NMDA antagonist, MK-801, were administered over 7 days by osmotic pumps stereotaxically implanted into the lateral ventricles of normal 10 day old rats. Alternatively, 10 and 20 day old rats received a 7 day course of intraperitoneal (i.p.) NBQX. One month later, the NBQX-, MK-801-treated rats, and controls underwent a series of behavioral studies: handling test, open field, and Morris water maze. Flurothyl inhalation was used to test seizure susceptibility in all groups. Although all of the rats treated with NBQX via osmotic pumps had spontaneous seizures, rats surviving infusion of EAAs had no deficits in learning, memory, or behavior and did not differ from controls in seizure susceptibility with flurothyl. In the developing animal, a short-term course of EAA antagonists leads to no long-term adverse effects on behavior or seizure susceptibility.
AB - Because of the critical role of excitatory amino acids (EAAs) in epileptogenesis and seizure-induced brain damage, EAA antagonists are now being considered as a possible therapy for seizures. However, during development EAAs play a pivotal role in learning, memory, and brain plasticity. To evaluate the long-term effects of a short course of EAA antagonists on the developing brain, a non-NMDA antagonist, NBQX, or a NMDA antagonist, MK-801, were administered over 7 days by osmotic pumps stereotaxically implanted into the lateral ventricles of normal 10 day old rats. Alternatively, 10 and 20 day old rats received a 7 day course of intraperitoneal (i.p.) NBQX. One month later, the NBQX-, MK-801-treated rats, and controls underwent a series of behavioral studies: handling test, open field, and Morris water maze. Flurothyl inhalation was used to test seizure susceptibility in all groups. Although all of the rats treated with NBQX via osmotic pumps had spontaneous seizures, rats surviving infusion of EAAs had no deficits in learning, memory, or behavior and did not differ from controls in seizure susceptibility with flurothyl. In the developing animal, a short-term course of EAA antagonists leads to no long-term adverse effects on behavior or seizure susceptibility.
KW - Animal model
KW - Behavioral test
KW - Brain damage
KW - Epilepsy
KW - Pilocarpine
KW - Seizure
KW - Status epilepticus
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U2 - 10.1016/0165-3806(96)00094-6
DO - 10.1016/0165-3806(96)00094-6
M3 - Article
C2 - 8874901
AN - SCOPUS:0030565440
SN - 0165-3806
VL - 95
SP - 256
EP - 262
JO - Developmental Brain Research
JF - Developmental Brain Research
IS - 2
ER -