EFFECTS OF CHRONIC NICOTINE AND PILOCARPINE ADMINISTRATION ON NEOCORTICAL NEURONAL DENSITY AND [H-3] GABA UPTAKE IN NUCLEUS BASALIS LESIONED RATS

We investigated the possible long-term neuroprotective roles of (-)nicotine and muscarinic agonist, pilocarpine, in the neocortices of rats receiving bilateral nucleus basalis lesions. Ibotenic acid-lesioned animals eventually displayed a 15-20% reduction in the density of neocortical Nissl staining neurons in layers II, III and VI, as well as a 27% loss in high-affinity GABA uptake 8 months post-lesioning. Deficits were not observed at earlier intervals. (-)Nicotine (0.2 mg/kg, i.p.) or (-)nicotine plus pilocarpine (1 mg/kg, i.p.) attenuated these losses when administered once daily to rats from 5-8 months post-lesioning. Pilocarpine alone had no protective effect on neuronal density or GABA uptake. These results suggest that nicotine receptor activation may counteract neocortical neuronal loss/atrophy following loss of ascending basal forebrain neurons.