The present study was aimed at assessing the influence of noradrenergic innervation of the paraventricular nucleus (PVN) and the arcuate nucleus (
ARC) of the brain hypothalamus on
cytochrome P450 expression in the liver.
DSP-4, a
neurotoxin specific to noradrenergic nerve terminals, was administrated locally into the PVN or
ARC. One week after
neurotoxin injection, the levels of neurotansmitters (
noradrenaline/
dopamine/
serotonin) were measured in the middle part of the hypothalamus,
hormone concentrations were estimated in blood plasma, and the activity and the
protein levels of CYP
isoforms were measured in the liver. A significant decrease in
noradrenaline level in the hypothalamus was observed after
DSP-4 injection into the PVN or
ARC. The levels of
dopamine or
serotonin remained unchanged or slightly lowered. Simultaneously, significant changes in the plasma concentration of
growth hormone were found; its elevation in PVN-lesioned rats and a drop in
ARC-lesioned ones. There were no changes in the plasma concentration of the
thyroid hormones or
corticosterone. The activity and
protein levels of
isoforms CYP2C11,
CYP3A and
CYP2A rose in the liver of PVN-lesioned rats, but the activity and
protein level of CYP2C11 fell in
ARC-lesioned animals such a tendency being also observed in the case of
CYP3A. Our study shows that noradrenergic innervation of the PVN and
ARC of the hypothalamus exerts an opposite effect on the regulation of
cytochrome P450 in the liver. These findings may be important for pharmacological experiments and
pharmacotherapy with neuroactive drugs, since
cytochrome P450 is responsible for the metabolism of
steroids and the majority of drugs.