Postnatal administration of anticonvulsant and sedative agents affects neurogenesis

Stefovska VG et al. (2008) Sedative and anticonvulsant drugs suppress postnatal neurogenesis. Ann Neurol 64: 434–445

The γ-aminobutyric acid subtype A (GABA_A) receptor agonists phenobarbital and diazepam, used as sedatives or anticonvulsants in newborn babies, and the N-methyl-D-aspartate (NMDA) receptor antagonist MK801 suppress early postnatal neurogenesis, a new study has revealed.

Stefovska et al. studied the effects of MK801, phenobarbital and diazepam on cell proliferation and neurogenesis in neonatal rat brains during the first three postnatal weeks. Wistar rat neonates were injected either with one of these agents or with saline solution (control); neurogenesis and cell proliferation were assessed by means of cell-type-specific markers and a compound that labels DNA during cell division.

Compared with the brains of the control rats, the numbers of proliferating cells were reduced in rat brains after treatment with MK801, phenobarbital or diazepam; the greatest reduction was observed in rats treated with MK801. Numbers of new cells in the brain were also reduced following administration of the NMDA antagonist or GABA_A agonists. This effect was not, however, a result of apoptosis; the authors instead suggested inhibition of proliferation as the causal factor. Postnatal neurogenesis, confined to the dentate gyrus in the brains of the study rats, was inhibited in the rats treated with MK801 and phenobarbital. Rats aged 6 months that previously received postnatal phenobarbital had impaired learning and reduced memory capacity in comparison with their saline-treated counterparts.

In light of these results, Stefovska and colleagues suggest that caution should be used when considering treatment with NMDA antagonists or GABA_A agonists in obstetric, neonatal or pediatric patients.