Abstracts

Developmental studies using brain preparations in vitro have suggested that neurotransmitter GABA exerts excitatory action on immature neurons. For example, in the neonatal rat hippocampal slices, drugs that enhance the postsynaptic action of GABA, such as diazepam, increase the amplitude and frequency of network driven Giant Depolarizing Potentials (GDPs)from birth till the postnatal day (P)10, when GABA switches from excitatory to inhibitory. However, it remains unknown when similar excitatory action of GABA takes place also in vivo. The purpose of the present study was to investigate the action of GABA on the neonatal rat hippocampal and neocortical neurons in vivo. Extracellular field and multiple unit activity (MUA) recordings Using extracellular field and multiple unit activity (MUA) recordings we found that diazepam and phenobarbital injected intraperiotaneally increase the frequency of the sharp waves in the hippocampus from P4-8 - but not adult - rats. In several cases we also observed interictal-like activity composed of single or multiple population spikes in P4-8 animals. Thus, positive allosteric GABA(A) modulators benzodiazepines and barbiturates enhance the excitability of the hippocampal network in vivo before P8, suggesting that GABA exerts excitatory action at the early developmental stages in vivo. This study raises concern on possible proconvulsive effects of GABAergic drugs in preterm infants. (Supported by INSERM.)