Important roles of N-methyl-D-aspartate receptors in expression of amygdaloid-kindled seizure demonstrated by intraperitoneal administration of L-aspartate in dimethyl sulfoxide.
Intraperitoneally (i.p.) administered L-aspartate (Asp) (20 mmol/kg) produced no behavioral or EEG change in nonkindled rats. Nonkindled rats that received 18, 19, or 20 mmol/kg Asp, dissolved in 10 or 15% dimethylsulfoxide (DMSO), i.p. developed masticatory movement, head nodding, and myoclonic jerks of the limbs, followed by wild running and subsequent tonic extension of the whole body. In contrast to the effects in nonkindled rats, i.p. injection of Asp 20 mmol/kg in 15% DMSO in amygdala-kindled rats precipitated electroclinical generalized seizures identical to kindled ones. When the kindled amygdala was pretreated with 2-amino-7-phosphonoheptanoic acid (2-APH), a potent and specific antagonist of N-methyl-D-aspartate (NMDA) receptors, the Asp/DMSO-induced generalized convulsion identical to kindled amygdala seizure was suppressed. 2-APH treatment of the contralateral amygdala was without such suppression. The results suggest that (a) Asp is ineffective when given alone (when given with DMSO, however, Asp evokes generalized seizures identical to kindled ones in amygdala-kindled rats, while it induces a qualitatively different generalized seizure in nonkindled rats; (b) NMDA receptors of the kindled amygdala play an important role in activation of the transsynaptic neurocircuit underlying the expression of kindled amygdala seizure; and (c) DMSO is useful in assessing potential central effects of compounds that do not readily penetrate the blood-brain barrier (BBB).
Mori
N
N
Department of Neuropsychiatry, Fukushima Medical College, Japan.
Wada
J A
JA
Sato
T
T
Saito
H
H
Kumashiro
H
H
D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001224:Aspartic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004338:Drug Combinations; D004569:Electroencephalography / Q000187:drug effects; D007839:Functional Laterality / Q000502:physiology; D007274:Injections, Intraperitoneal; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000209:etiology*
D004338:Drug Combinations; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D004121:Dimethyl Sulfoxide