Serotonin 1A sub-type receptors play an important role in the
etiopathogenesis of depression, which is known to occur more often in
females than males. Early experiences can be a predisposing factor for
depression; however, the underlying cellular processes remain unknown.
In an effort to address such issues, we employed neonatal handling, an
experimental model of early experience, which has been previously shown
to render females more vulnerable to display enhanced depression-like
behavior in response to chronic stress, while it increases the ability
of males to cope. In rat pre-pubertal (30 days of age) and adult (90
days) hippocampus, of both males and females, the effect of neonatal
handling on serotonin 1A sub-type receptor mRNA and protein levels was
determined by in situ hybridization and immunohistochemistry,
respectively, while the number of binding sites was determined by in
vitro autoradiography using [H-3]8-hydroxy2(di-n-propylamino)tetralin
as the ligand. Our results revealed a significant sex difference in
serotonin 1A sub-type receptor mRNA, protein and binding sites, with
females having higher levels than males. Handling resulted in
statistically significant decreased numbers of cells positive for
serotonin 1A sub-type receptor mRNA or protein, as well as
[H-3]8-hydroxy-2(di-n-propylamino)tetralin binding sites in the area 4
of Ammon’s horn and dentate gyrus of both pre-pubertal males and
females. In adult animals the number of serotonin 1A sub-type receptor
mRNA positive cells was increased as a result of handling in the area I
of Ammon’s horn, area 4 of Ammon’s horn and dentate gyrus of males,
while it was decreased only in the area 4 of Ammon’s horn of females.
Furthermore, the number of serotonin sub-type 1A receptor immunopositive
cells, as well as [H-3]8-hydroxy-2(di-n-propylamino)tetralin binding
sites was increased in the area 1 of Ammon’s horn, area 4 of Ammon’s
horn and dentate gyrus of handled males, whereas it was decreased in
these same brain areas in the handled females. We can thus infer that
neonatal handling results in alterations in postsynaptic serotonergic
neurotransmission, which may contribute to the sex dimorphic effects of
handling as to the vulnerability toward depression-like behavior in
response to chronic stressful stimuli. (c) 2006 Published by Elsevier
Ltd on behalf of IBRO
