P. Tirassa et al., CHOLECYSTOKININ-8 REGULATION OF NGF CONCENTRATIONS IN ADULT-MOUSE BRAIN THROUGH A MECHANISM INVOLVING CCKA AND CCKB RECEPTORS, British Journal of Pharmacology, 123(6), 1998, pp. 1230-1236
1 Nerve growth factor (NGF), a powerful agent for the growth, differen
tiation and regeneration of lesioned cells of the central and peripher
al nervous systems, has in recent years been indicated as a potential
therapeutic agent capable of reversing the processes of cell damage in
neurodegenerative events in man. Since NGF does not cross the blood-b
rain barrier and central NGF administration requires invasive surgical
procedures, the discovery of substances modulating in vivo NGF synthe
sis in the brain will be extremely useful for a possible clinical use
of NGF. 2 The aim of the present study to analyse if the content of NG
F in the brain of adult mice can be affected by peripheral administrat
ion of cholecystokinin-8 (CCK-8), a well known neuropeptide which has
stimulant actions on neurons in the brain and promotes a variety of ne
urobehavioural effects both in man and rodents. 3 The dose-response an
d time course effects of an i.p. injection of CCK-8 on the NGF concent
rations in the hippocampus, cortex. hypothalamus and pituitary of adul
t male mice were analysed by use of a sensitive immunoenzymatic assay
for NGF. The effects of pretreatment with selective CCKA and CCKB rece
ptor antagonists and atropine on the NGF response to CCK injection wer
e also studied. 4 The effects of CCK-8 were dose-and time-dependent an
d the injection of 8 nmol kg(-1) resulted in a 3 fold increase of NGF
levels in the hypothalamus and pituitary, and about a 60% increase in
the hippocampus. No effects were observed in the cortex. Pretreatment
with a selective CCKA receptor antagonist blocked the CCK-induced NGF
increase in the hypothalamus and pituitary. In the hippocampus the sam
e effect was obtained with a CCKB receptor antagonist. Pretreatment wi
th atropine suppressed the CCK-induced effects on NGF levels in all th
e brain regions examined. 5 Our results showing that i.p. injection wi
th CCK-8 can modulate NGF levels in the brain through a mechanism whic
h seems, in part, to be mediated via the vagal afferents, indicate tha
t this neuropeptide may represent a useful pharmacological approach to
enhance endogenous NGF levels in neuropathologies associated with a n
eurotrophin deficit.