Nicotine-induced escalation of ethanol intake - an effect mediated by the vagus nerve

Abstract

Abstract Supervisor: Docent Mia Ericson Author: Fahim Sharan Nicotine-­‐induced escalation of ethanol intake-­‐ an effect mediated by the vagus nerve? There is a clear connection between alcohol abuse and smoking. Previous studies show that 83% of those with alcohol abuse also smoke and that alcoholism is 10 times more common in smokers than in non-smokers. This clinical observation also finds support in pre-clinical animal studies where nicotine treatment has shown to increase ethanol intake in rats. Current research shows that central nicotinic acetylcholine receptors (nAChR) play a vital role in the dopamine releasing effects of ethanol. However, other studies have demonstrated that blockade of peripheral ganglionic nAChR invokes some kind of adaptations, which in turn escalates ethanol intake. We have reason to believe that both peripheral and central nAChR are involved in ethanol consumption. Since the vagus nerve receives input via nAChRs and is a big contributor to the autonomic nervous system, our hypothesis is that this nerve mediates the nicotine-induced escalation of ethanol intake. Thus this present study focused on designing a method that allowed us to surgically ligate certain branches of the vagus nerve in the rat thus removing the peripheral nAChR influence of ethanol intake. If we manage to establish a successful method we will later be able to let vagotomized rats undergo an ethanol-consumption study where we can evaluate if the abolished influence of the vagus nerve changes nicotine-induced escalation of ethanol intake. A total of 16 animals across 4 trials were operated on during the course of this study. 6 animals were judged to have a successful vagotomy, resulting in a 40% success rate for the surgical procedure. However, we faced great challenges with stabilizing the animals in the post-operative phase due to persisting weight loss, but were finally successful in stabilizing the weight in trial 4 with a liquid diet. All in all, we managed to achieve a successful gastric vagotomy with a stable post-operative weight gain in only 1 animal of the 16 operated. Conclusively, more surgical practice is needed before achieving an optimal method. However, we believe that with practice, a higher success rate of vagotomy can be achieved and along with a post-operative diet based on liquid diet we will have vagotomized animals stable enough to undergo a voluntary ethanol intake paradigm. Key words: Ethanol intake, nicotine, vagus nerve, vagotomy.