Long-lasting effects of neonatal pentobarbital administration on spatial learning and hippocampal synaptic plasticity.

Abstract:

:Exposure of newborn rats to antiepileptics such as barbiturates has long-lasting detrimental effects on the hippocampus and hippocampus-dependent behavior. However, the long-term consequences of neonatal administration with barbiturates on the hippocampal synaptic plasticity remain unresolved. In this study, we investigated the long-lasting effects of a neonatal administration of pentobarbital on spatial memory, paired-pulse plasticity in the population spikes, and long-term potentiation (LTP) in the hippocampal CA1 region of rats in vivo. Eight weeks after administration of pentobarbital (10 or 20mg/kg) on the seventh postnatal day (P7), rats showed impaired induction in LTP. During paired-pulse stimulation, pentobarbital-treated rats exhibited a greater facilitation of the test pulse population spike, suggesting a disruption in the inhibitory GABAergic synaptic transmission. Spatial learning in hidden platform task of the Morris water maze was impaired in pentobarbital-treated rats. Our present findings indicate that neonatal treatment with pentobarbital causes alterations in function of the hippocampal inhibitory synaptic transmission that persist into adulthood, likely contributing to the long-lasting abnormalities in the hippocampal LTP as well as learning ability. We also demonstrated significant respiratory disturbances, i.e., severe hypoxia, hypercapnia, and extracellular acidosis, in rats treated with pentobarbital on P7. Given that extracellular acidosis can also modulate synaptic transmission in the developing hippocampus, this finding led us to speculate regarding the influence of respiratory disturbances in pentobarbital-induced long-lasting hippocampal dysfunctions.

journal_name

Brain Res

journal_title

Brain research

authors

Tachibana K,Hashimoto T,Kato R,Tsuruga K,Ito R,Morimoto Y

doi

10.1016/j.brainres.2011.02.086

subject

Has Abstract

pub_date

2011-05-04 00:00:00

pages

69-76

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(11)00465-3

journal_volume

1388

pub_type

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