Exposure to Nicotine and Withdrawal in Wistar Rats: An Electrophysiological Study
Authors: da SilvaTiago Allan Carlos , Fonseca Suzane Maia da , Padilha da Silveira Esther , Santos Vitoria Corrêa , Campos Fernanda Myllena Sousa , Carvalho de Lima Danielma , Obara Mariana Kondo , Ribeiro Rafaella Marques , Rodrigues João Cleiton Martins , Reis Marcos Vinícius Cardoso , Hamoy Maria Klara Otake , Castro Josuelem Portela , Gomes Leal Walace , Favacho Lopes Dielly Catrina , Hamoy Moisés 
Published: October 2024

Abstract

Introduction
Throughout the world, smoking is one of the principal causes of preventable death. Nicotine, the primary active component of tobacco, acts as a psychostimulant, and modulates the electrical activity of a number of the areas of the brain involved in addiction. Abstinence from nicotine will also impact the functional state of the brain, which is reflected in symptoms of craving and susceptibility to relapse. In addition, given the increase in the sympathetic tone of the heart and pulse rate promoted by nicotine, its consumption can contribute to tachyarrhythmia.

Methods
The present study investigated the electroencephalographic (EEG) and electrocardiographic (ECG) patterns of Wistar rats submitted to acute or chronic exposure to nicotine, followed by withdrawal for 24 or 48 h, and the re-administration (or not) of nicotine, to simulate episodes of relapse.

Results
The EEG data revealed an increase in all types of brainwaves, with emphasis on high-frequency (alpha, beta, and gamma) brain oscillations following both acute and chronic exposure to nicotine (14 days), whereas in withdrawal, there was a predominancy of delta waves. When exposure to nicotine was reinstated after withdrawal, the observed EEG profile was similar to that found in chronic exposure. The electrocardiogram reads showed that both acute and chronic exposure to nicotine caused abnormalities in the atrioventricular conduction and that, while these changes improve with substance withdrawal, relapse can worsen these parameters.

Conclusions
The results of this study indicate that high-frequency brainwaves are correlated with nicotine dependence, while slow brain oscillations are consistent with drug craving, and episodes of nicotine relapse can reproduce brain activity patterns linked to dependence. Finally, exposure to nicotine predisposes the individual to heart rhythm abnormalities, which are attenuated by withdrawal, but may nevertheless be restored rapidly with re-exposure to the substance.

Implications
This study demonstrated that nicotine increases high-frequency brain oscillations, which is associated with addiction, whereas withdrawal elevates the delta wave power, suggesting craving. Re-exposure to nicotine following withdrawal restores rapidly the EEG profile of chronic dependence. In addition, nicotine has deleterious impacts on cardiac activity, which are linked to fatal arrhythmias. This implies that stopping smoking is beneficial for the amelioration of the alterations in heart rhythm caused by nicotine addiction. This study elucidates the functional states of the brain and heart during both sporadic and chronic nicotine use, and the electrophysiological explanation for substance dependence and drug relapse after craving episodes.