Neonatal 6-hydroxydopamine treatment affects GABA(A) receptor subunit expression in the frontal cortex but not the hippocampus of rats during postnatal development.

ABSTRACT

The influence of neonatal administration of 6-hydroxydopamine (6-OHDA) on the maturation of GABA(A) receptors in the frontal cortex and hippocampus was studied using 5- to 40-day-old rats. In situ hybridization with antisense oligonucleotide probes was performed for alpha(1), alpha(2), alpha(5), beta(2), beta(3) and gamma(2) subunit mRNAs of the GABA(A) receptor. We demonstrated that neonatal treatment with 6-OHDA temporarily delays the postnatal transcription of the alpha(1) and gamma(2) subunits in the rat prefrontal cortex, as assessed by in situ hybridization histochemistry. The effect was selective for these subunits (the alpha(2), alpha(5), beta(2), and beta(3) subunit mRNAs remained unchanged) and for this region (the mRNA levels in the hippocampus were not changed). The reduction in mRNA levels at early postnatal stages (postnatal day 5, PD5, and PD10) also affected the subunit protein levels, as shown by immunohistochemistry for the alpha(1) subunit, and the formation of GABA(A) receptor-associated picrotoxinin-insensitive TBPS binding sites, as shown by autoradiography. Our findings indicate that without a noradrenergic influence, the maturation of GABAergic interneurons in the frontal cortex is transiently delayed (from PD5 to PD40). However, it is possible that this transient reduction of the expression of certain GABA subunits - caused by depletion of noradrenergic innervation - cannot cause a lasting alteration to the GABAergic function in the prefrontal cortex.