Rat pups exhibit transient "developmental
dyskinesias," such as
tremor and
myoclonus, that are analogous to motor immaturities of the human neonate.
Myoclonic jerks in the neonatal rat may reflect a developmental imbalance of excitatory and inhibitory neurotransmission. To test this hypothesis, spontaneous
myoclonic jerks of naive rat pups (n = 200) were characterized behaviorally and pharmacologically. The frequency of
myoclonus was high (154 +/- 14 jerks/30 min) in the first week. The distribution of jerks included limbs (47%) (27% in forelimbs and 20% in hindlimbs), tail (30%), trunk (12%), and head (11%).
Myoclonus constituted the predominant neonatal adventitious movement (81%).
Myoclonic jerks were variable in intensity, focal and multi-focal more often than generalized, and occurred when nonrespiratory movements were infrequent or absent, suggesting sleep. Myoclonic frequency significantly diminished after the second week; therefore,
drug effects were studied in the first 7 days. Systemic injection of the novel noncompetitive
N-methyl-D-aspartate (
NMDA) receptor antagonist
MK-801 blocked neonatal
myoclonus in a dose-dependent manner (ID50 = 0.67 mg/kg; r = 0.93). The nonselective
excitatory amino acid (EAA) receptor antagonist
kynurenic acid was ineffective. The EAA antagonist AP4 (1 and 10 mg/kg) also reduced
myoclonic jerks, but other drugs, such as the selective
glycine antagonist
Iso-THAO (1 and 10 mg/kg),
strychnine (0.5 mg/kg),
clonazepam, and
diazepam (1 mg/kg), were ineffective blockers. The putative agonists
quisqualic acid (1-50 mg/kg) and
NMDA (1-10 mg/kg) altered
myoclonus only at behaviorally toxic doses. These data suggest that EAA receptors participate in developmental
myoclonus of the neonatal rat and that development
myoclonus may be a useful quantitative model of functional maturity of excitatory/inhibitory synapses. The efficacy of
MK-801 also should be evaluated in
drug- and lesion-induced
myoclonus. Recognition of the high frequency and state dependence of spontaneous
myoclonic jerks in neonatal rats may be important to neonatal
antiepileptic drug studies.