Cellular mechanisms underlying the effect of a single exposure to neonatal handling on neurotrophin-3 in the brain of 1-day-old rats.

Neurotrophin-3 (NT-3) has an important role in brain development and is thus a good candidate molecule to be involved in the cellular mechanisms mediating the effects of early experiences on the brain. In the present work we employed the model of neonatal handling, which is known to affect the ability of the adult organism to respond to stressful stimuli, and determined its effects on NT-3 levels in the rat hippocampus and cortex 2, 4 and 8 h after handling on postnatal day 1. We also recorded maternal behavior during the 8 h following handling. At both the 4 and 8 h time-points there was an increase in NT-3 positive cells in field 1 of Ammon's horn (CA1 area of the hippocampus) and parietal cortex of the handled animals. In the parietal cortex NT-3 levels increased with time following handling: at 8 h there were more NT-3 positive cells than at 4 h. During the 4 h following the end of handling, handled pups were subject to more maternal licking, indicating that the more intense maternal care could underlie the handling-induced increase in NT-3. In the hippocampus, the handling induced increase in NT-3 was cancelled by inhibition of N-methyl-D-aspartate (NMDA), AMPA/kainate, or GABA-A receptors, as well as L-type voltage-gated Ca(2+) channels. It thus appears that neonatal handling activates these neurotransmitter receptors and channels, leading to increased intracellular Ca(2+) and increased NT-3 expression. NT-3 can then activate downstream effectors and exert its morphogenetic actions and thus imprint the effects of handling on the brain.