Basal forebrain stimulation induces NGF secretion in ipsilateral parietal cortex via nicotinic receptor activation in adult, but not aged rats

The role of cholinergic basal forebrain inputs to cerebral cortex in regulating regional nerve growth factor (NGF) secretion was examined in adult (4-6 months) and aged (29-31 months) rats. Halothane-anesthetized rats received unilateral electrical stimulation of the nucleus basalis of Meynert (NBM). NGF levels were measured by ELISA in samples from a microdialysis probe in the parietal cortex, while measuring blood flow. In adult and aged rats, NBM stimulation (for 100 min) increased blood flow ipsilaterally during stimulation by 55% and 25%, respectively. In adult, but not aged rats, NGF levels were significantly increased ipsilaterally (up to 68%) over prestimulus levels at 200-500 min after stimulation ended. The cellular localization of NGF-like immunoreactivity showed no differences between the cortices with and without NBM stimulation. The NGF response was abolished by the nicotinic blocker, mecamylamine (20 mg/kg iv), but unaffected by the muscarinic blocker, atropine (5 or 25 mg/kg iv). Both drugs reduced the blood flow responses. We conclude that cholinergic inputs to neocortex mediate NGF secretion by cortical neurons via nicotinic receptors. Further, the absence of this response in aged rats suggests a decline in the number or activity of cortical nicotinic receptors.