Effect of chronic nicotine administration on the anterior cingulate cortex (area 24a) of adult albino rats: a histological and immunohistochemical study

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Nicotine is the principal active component in cigarettes and cigars. It was reported that tobacco smoking enhances the performance of cognitive processing. The anterior cingulate cortex plays an important role in attention and working memory performance.

Aim of the work

This study was conducted to demonstrate the effects of chronic administration ofvarious nicotine doses on the structure of the ventral anterior cingulated cortex (area 24a) in adult rats, as well as study the effect of withdrawal of high doses of nicotine.

Materials and methods

A total of 48 adult male albino rats were used. They were divided into four groups. Group I (n=12) was considered the control group. Group II (n=12) rats were treated with 1 mg/kg nicotine subcutaneously for 2 months. Group III rats (n=24) were treated with 6 mg/kg nicotine subcutaneously for 2 months. Thereafter, half of the animals were sacrificed. Group IV (the recovered group) consisted of the remaining 12 rats of group III that were kept for another 2 months without treatment and then sacrificed. Brains were processed to be studied using Einarson’s gallocyanin stain, the Golgi–Cox method, transmission electron microscopy, and immunohistochemical study for glial fibrillary acidic protein (GFAP). Further, the number of cells in the second and fifth layers of the cingulate cortex (area 24a) was measured and statistically analyzed for all the studied groups.


Examination of the cingulate cortex (area 24a) in low-dose nicotine-treated rats (group II) revealed an increase in the branching of the dendrites of the pyramidal cells together with a relative increase in the density of the spines. An ultrastructural study showed the presence of numerous synaptic contacts between the nerve processes. In high-dose nicotine-treated rats (group III) the cells showed degenerative changes, which were more evident in pyramidal cells. These changes were associated with a marked reduction in the extension and branching of the dendrites. Dense GFAP immunostained fibers and cells could be seen particularly in layer I. In the recovered rats (group IV) most of the cells restored their normal appearance. Mild GFAP expression could be observed. An insignificant difference in the number of cellswas also found in comparison with controls.


The effect of nicotine on the organization of the anterior cingulate cortex (area 24a) was found to vary according to dose. Withdrawal of high doses of nicotine will result in a marked reduction in the structural impairment of neurons.

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