GABA, benzodiazepine and serotonergic receptor development in the dorsal raphe nucleus: electrophysiological studies

To assess potential differences in the functional responsiveness of GABAergic and serotonergic receptors during postnatal development, extracellular recordings were made in in-vitro midbrain slices containing the dorsal raphe nucleus (DRN). Pacemaker-like activity analogous to that observed in vivo was induced by superfusing the slices with 2.5 microM phenylephrine. GABA (0.001 M) and 5-HT (0.004 M) dissolved in 0.1 M NaCl were applied microiontophoretically for 1-min intervals using a range of iontophoretic currents. The current required to produce a 50% inhibition in firing was determined using logit and regression procedures. Iontophoretically applied picrotoxin, baclofen, and bicuculline were applied alone and in combination with GABA to characterize the neonatal GABA receptor site. The pharmacology of the GABA responses observed in early postnatal DRN neurons was that associated with the GABAA subtype. No significant changes in sensitivity to iontophoretically applied 5-HT or GABA were observed at any time during postnatal development. The application of the benzodiazepine, clonazepam, in the perfusion fluid at doses between 10(-8) and 10(-7) potentiated the inhibitory effects of GABA in the slices, but produced no consistent inhibitory effect by itself. The increased potentiation of GABA's effects by benzodiazepine was greatest in neonatal animals. This finding is consistent with previous literature showing enhanced coupling of the GABA-benzodiazepine complex at early postnatal ages.