Atorvastatin improves Y-maze learning behaviour in nicotine treated male albino rats

• Nicotine reduces learning ability by activating multiple pathways.
• Co-administration of nicotine with statin improved learning ability.
• The mechanism may be by reduction of ROS and improvement in membrane integrity.
• It resulted in enhanced expression of NMDA–R, and monoamine oxidases.
• Alterations in the neurotransmitter levels might have improved neural functions.

Nicotine is a parasympathomimetic alkaloid present in tobacco which can induce hyperlipidemia and has a direct effect on neural functions. Statins, competitive inhibitors of 3-hydroxymethyl-3-glutaryl-coenzyme-A reductase, are cholesterol lowering drugs. It has some neuroprotective effects. Hence we analysed the combined effect of nicotine and statin on the learning behaviour of male albino rats. We employed Y-Maze conditional discrimination task. Rats were divided into 4 groups with six rats in each group. (1) Control, (2) Atorvastatin (10 mg/kg b.wt), (3) Nicotine (0.6 mg/kg b.wt) and (4) Atorvastatin (10 mg/kg b.wt) + Nicotine (0.6 mg/kg b.wt). After 30 days of treatment rats from each group were selected for behavioural study and they were observed for 30 days. At the end of the experimental period rats were sacrificed, and brain and liver were dissected out for further biochemical analysis. Nicotine treated group showed least performance in learning in comparison with control, atorvastatin and atorvastatin + nicotine treated groups. Co-administration of atorvastatin and nicotine improved learning behaviour compared to nicotine treated group. Reactive oxygen species level was significantly increased in nicotine group compared to control. The level of neurotransmitter serotonin which has a significant role in learning was found to be decreased in nicotine treated group compared to the control group. Activity of Na+ K+ ATPase, Ca2 + ATPase and glutathione content was significantly reduced in nicotine treated group compared to control. The activity of acetylcholine esterase was significantly increased in the nicotine treated group. Expression studies showed significant decrease in N-methyl D-aspartate receptors and increase in mono amine oxidase-A and mono amine oxidase-B in nicotine treated group and was reversed in atorvastatin + nicotine treated group. It can be concluded that co-administration of nicotine with statin ameliorates the neural functional alterations caused by nicotine to a significant level.