Chronic memantine decreases nicotine self-administration in rats.

Abstract

Neurobehavioral bases of tobacco addiction and nicotine reinforcement are complex, involving more than only nicotinic cholinergic or dopaminergic systems. Memantine is an NMDA glutamate antagonist used to improve cognitive function in people with Alzheimer's disease. Glutamate may be an important component of the reinforcing effects of nicotine, so memantine was evaluated as a potential smoking cessation aid. Two studies were conducted with adult female rats, one testing acute effects of memantine over a range of doses for changing nicotine self-administration and the other testing the chronic effects of memantine to reduce nicotine self-administration. Acute memantine injections slightly, but significantly, increased nicotine self-administration in a dose-related manner. In contrast, chronic memantine treatment significantly reduced nicotine self-administration. During the first day of memantine administration in the chronic study, nicotine self-administration was significantly elevated replicating the acute study. Starting in the second week of treatment there was a significant reduction of nicotine self-administration relative to controls. This was seen because memantine treatment prevented the increase in nicotine self-administration shown by controls. There even continued to be a memantine-induced lowered nicotine self-administration during the week after the cessation of memantine treatment. Memantine or other drugs affecting NMDA glutamate receptors may be useful aids to smoking cessation. Full efficacy for reducing nicotine self-administration was seen as the NMDA drug treatment is given chronically. Importantly, the effect persisted even after treatment is ended, indicating the high potential for NMDA glutamate receptors to impact nicotine addiction.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1016/j.ejphar.2019.172592

Publication Info

Levin, Edward D, Corinne Wells, Leah Yao, Wendi Guo, Anica Nangia, Sarah Howard, Erica Pippen, Andrew B Hawkey, et al. (2019). Chronic memantine decreases nicotine self-administration in rats. European journal of pharmacology, 861. p. 172592. 10.1016/j.ejphar.2019.172592 Retrieved from https://hdl.handle.net/10161/29509.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.