CHRONIC NICOTINE TREATMENT PREVENTS NEURONAL LOSS IN NEOCORTEX RESULTING FROM NUCLEUS BASALIS LESIONS IN YOUNG-ADULT AND AGED RATS

In both young adult and aged rats, we tested the ability of chronicall y administered nicotine to rescue neocortical neurons from transneuron al degeneration resulting 5 mo after ibotenic acid (IBO) lesioning of the nucleus basalis magnocellularis (NBM). Young adult (2-3 mo-old) an d aged (20-22-mo-old) rats were given unilateral infusions of IBO (5 m u g/1 mu L) at two sites within the NBM. Following surgery, animals be gan receiving either daily ip injections of nicotine (0.2 mg/kg) or sa line vehicle. Treatment continued for 5 mo, at which time all animals were sacrificed and their brains processed histologically. For each br ain, computer-assisted image analysis was then used to analyze the unl esioned (left) and lesioned (right) side of five nonconsecutive brain sections from parietal cortex Layers II-IV and V. NBM lesioning in bot h young adult and aged vehicle-treated rats resulted in a significant 16-21% neuronal loss ipsilateral to NBM lesioning in neocortical Layer s II-IV. Aged NBM-lesioned rats also exhibited a significant 12% neuro nal loss in neocortical Layer V ipsilaterally. By contrast, those NBM- lesioned young adult and aged rats that received daily nicotine treatm ent postsurgery did not show any ipsilateral neuronal loss in the same parietal cortex areas, indicating that chronic nicotine treatment pre vented the transneuronal degeneration of neocortical neurons resulting 5 mo afer NBM lesioning. Nicotine treatment alone did not have any ef fect on neuronal density, neuronal size, or glial cell numbers in the neocortex. The neuroprotective/neurotrophic action of nicotine in the neocortex following NBM lesions may involve activation of pre- and/or postsynaptic nicotinic receptors to maintain depolarizing influences o r neurotrophin synthesis, or it may involve nicotine's ability to incr ease glucose utilization and cerebral blood flow.