Study results demonstrate that nicotine use increases compulsive alcohol consumption

By Al Saint Jacques, MDLinx
Published December 17, 2015

Key Takeaways

The relationship between alcohol consumption and nicotine use should not come as a surprise as they are probably the two most co-abused drugs in the world. A recent study tested this relationship to determine whether use of nicotine does indeed facilitate a transition to alcohol dependence. The researchers, from institutions in Sao Paulo, Brazil; La Jolla, California; and Baltimore, Maryland, confirmed that nicotine and activation of nicotinic receptors are critical factors in the development of alcohol dependence through the dysregulation of a set of interconnected neuronal ensembles throughout the brain.

Previous studies have shown that nicotine can increase alcohol drinking in nondependent rats, yet it is unknown whether nicotine facilitates the transition to alcohol dependence. Researchers tested the hypothesis that chronic nicotine will speed up the escalation of alcohol drinking in rats and that this effect will be accompanied by activation of sparsely distributed neurons (neuronal ensembles) throughout the brain that are specifically recruited by the combination of nicotine and alcohol.

In the study, rats were trained to respond for alcohol and made dependent using chronic, intermittent exposure to alcohol vapor, while receiving daily nicotine (0.8 mg/kg) injections. Identification of neuronal ensembles was performed after the last operant session, using immunohistochemistry.

Results demonstrated that nicotine produced an early escalation of alcohol drinking associated with compulsive alcohol drinking in dependent, but not in nondependent rats (air exposed), as measured by increased progressive-ratio responding and increased responding despite adverse consequences. The combination of nicotine and alcohol produced the recruitment of discrete and phenotype-specific neuronal ensembles (∼4–13% of total neuronal population) in the nucleus accumbens core, dorsomedial prefrontal cortex, central nucleus of the amygdala, bed nucleus of stria terminalis, and posterior ventral tegmental area.

“It’s a vicious cycle,” said TSRI biologist Olivier George, a senior author of the new study. “Nicotine makes individuals crave alcohol to ‘reward’ the brain and reduce stress.”

Study authors showed that blockade of nicotinic receptors using mecamylamine (1 mg/kg) prevented both the behavioral and neuronal effects of nicotine in dependent rats. These results confirm that nicotine and activation of nicotinic receptors are critical factors in the development of alcohol dependence through the dysregulation of a set of interconnected neuronal ensembles throughout the brain.

“Now we can try to find compounds that will specifically inactivate those neurons,” said George.

Study authors included Rodrigo M. Leão of the Laboratory of Pharmacology, Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, Universidade Estadual Paulista - UNESP, Araraquara, Sao Paulo, Brazil; the Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute in La Jolla, California; and the Behavioral Neuroscience Branch, IRP/NIDA/NIH/DHHS in Baltimore, Maryland; Cleopatra S. Planeta of the Laboratory of Pharmacology, Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, Universidade Estadual Paulista - UNESP; Giordano de Guglielmo, Marian L. Logrip, George F. Koob, and Olivier George of the Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute in La Jolla, California; Leandro F. Vendruscolo of both the Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute in La Jolla, California, and the Behavioral Neuroscience Branch, IRP/NIDA/NIH/DHHS in Baltimore, Maryland; as well as Fábio C. Cruz and Bruce T. Hope of the Behavioral Neuroscience Branch, IRP/NIDA/NIH/DHHS in Baltimore, Maryland.

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