Related Experiment Video
Updated: Mar 12, 2026

Investigating Drivers of Antireward in Addiction Behavior with Anatomically Specific Single-Cell Gene Expression Methods
Published on: August 4, 2022
Withdrawal from Chronic Nicotine Exposure Produces Region-Specific Tolerance to Alcohol-Stimulated GluA1
M Adrienne McGinn1, Rod I Paulsen1, Christy A Itoga1
1Department of Physiology, Alcohol & Drug Abuse Center of Excellence, Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Background:
Nicotine use increases alcohol drinking, suggesting that the combination of these drugs may produce synergistic effects in activating reward circuitry. Alternatively, use of either of these drugs may facilitate the development of cross-tolerance to the other to promote intake escalation.
Methods:
In this study, adult male Wistar rats were chronically exposed to room air or chronic, intermittent nicotine vapor, which has been shown to produce symptoms of nicotine dependence as evidenced by elevated nicotine self-administration and a host of somatic and motivational withdrawal symptoms. We examined regional neuroadaptations in nicotine-experienced versus nonexperienced animals, focusing on changes in phosphorylation of the AMPA glutamate channel subunit GluA1 in reward-related brain regions as excitatory neuroadaptations are heavily implicated in both alcohol and nicotine addiction.
Results:
During withdrawal, nicotine exposure and alcohol challenge (1 g/kg) interactively produced neuroadaptations in GluA1 phosphorylation in a brain region-dependent manner. Alcohol robustly increased protein kinase A-mediated phosphorylation of GluA1 at serine 845 in multiple regions. However, this neuroadaptation was largely absent in 3 areas (dorsomedial prefrontal cortex, dorsal striatum, and central amygdala) in nicotine-experienced animals. This interactive effect suggests a molecular tolerance to alcohol-stimulated phosphorylation of GluA1 in the context of nicotine dependence.
Conclusions:
Nicotine may modify the rewarding or reinforcing effects of alcohol by altering glutamate signaling in a region-specific manner, thereby leading to increased drinking in heavy smokers.
More Related Videos
05:12Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder
Published on: June 23, 2023
15:27Construction of Vapor Chambers Used to Expose Mice to Alcohol During the Equivalent of all Three Trimesters of Human Development
Published on: July 13, 2014
Related Concept Videos
CNS Depressants: Alcohol and Nicotine
Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating...
Desensitization and Tachyphylaxis
Drug Dependence
Drug Abuse and Addiction: Pharmacological Phenomena