Chronic treatment with scopolamine and physostigmine changes nerve growth factor (NGF) receptor density and NGF content in rat brain.
Nerve growth factor (NGF) and NGF receptors were measured in cortex and hippocampus of rats treated with drugs affecting cholinergic neurotransmission. High (Kd = 0.045 nM) and low (Kd = 21 nM) affinity 125I-NGF binding sites were present in both cortical and hippocampal membranes with hippocampus containing higher numbers of both sites than cortex. Chronic treatment of rats with the muscarinic receptor antagonist scopolamine (5 mg/kg, twice daily) decreased the density of high- and low-affinity sites by 50-90% in cortical and hippocampal membranes. These changes were seen after 7 days, but not 3 days, of scopolamine treatment. Chronic infusion of physostigmine (1 mg/kg/day) using minipumps increased the number of high- and low-affinity sites in cortex 3- and 6-fold, respectively. The changes in receptor-binding parameters induced by physostigmine were transient as they were evident after 3 days of treatment, but returned to control levels after 7 days. NGF content in cortex and hippocampus was reduced by about 50% following 7, but not 3, days of chronic physostigmine infusion. In contrast, scopolamine treatment failed to change NGF levels in the cholinergic neuronal target regions but it decreased NGF content in the septal area. The content of NGF mRNA in the cortex measured by Northern blot analysis failed to change following either scopolamine or physostigmine treatment. The results suggest that the levels of NGF and NGF receptors in the target regions of cholinergic neurons are regulated by the extent of cholinergic neurotransmitter activity.
Alberch
J
J
Fidia-Georgetown Institute for the Neurosciences, Georgetown University Medical School, Washington, DC 20007.
Carman-Krzan
M
M
Fabrazzo
M
M
Wise
B C
BC
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D010277:Parasympathomimetics / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor; D012601:Scopolamine / Q000494:pharmacology*; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D009414:Nerve Growth Factors; D010277:Parasympathomimetics; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D010830:Physostigmine; D012601:Scopolamine