Assessing alcohol and nicotine co-consumption in mice

Alcohol and nicotine addiction are frequently co-morbid and share common genetic factors and molecular mechanisms, such as the involvement of the nicotinic acetylcholine receptors [1]. Epidemiological studies show that the consumption of alcohol can influence the consumption of nicotine, and vice versa, indicating that interactions between alcohol and nicotine use are important in their co-abuse [1]. However, very few animal models of alcohol and nicotine addiction employ voluntary self-administration of both drugs and are therefore unable to examine these interactions. The majority of studies have assessed the effect of passive administration of nicotine on alcohol consumption with conflicting results. Whether passive nicotine administration increases or decreases alcohol consumption depends on factors such as the dose of nicotine, the duration of alcohol exposure, and the timing of the nicotine injection relative to measuring alcohol consumption. While these important experiments highlight the overlap in addiction mechanisms between alcohol and nicotine, the models that utilize passive drug administration are not as relevant to human alcohol and nicotine co-addiction, as the drugs are voluntarily consumed and the amount consumed is self-titrated in humans. Another disadvantage of passive drug administration is that it can result in different molecular effects compared with voluntary consumption, such as reduced drug-induced dopamine release [2]. While oral nicotine and alcohol consumption have been examined separately in mice and rats, at the time of this publication there were no models of voluntary oral alcohol and nicotine co-consumption in mice. To capture the molecular and behavioral interactions that occur with voluntary alcohol and nicotine consumption, we developed a method for assessing chronic, voluntary oral alcohol and nicotine co-consumption in mice [3]. In our procedure, mice are presented with three separate bottles containing either alcohol, nicotine, or water in a " 3-bottle choice " experiment, without initial food or water deprivation. After chronic, intermittent access to alcohol and nicotine, the mice show somatic signs of withdrawal, indicating that they develop physical dependence from voluntary drug consumption, which shows we can produce physical dependence in mice without the use of forced drug consumption. Other advantages of our model are that we are able to investigate how the presence of one drug influences the consumption of the other drug, how enforced alcohol abstinence affects concurrent nicotine consumption, and how re-introduction of alcohol after abstinence affects consumption of both drugs. We observe drug consumption patterns that are similar to those seen in studies utilizing voluntary alcohol …