Biological processes underlying co-use of alcohol and nicotine: neuronal mechanisms, cross-tolerance, and genetic factors

Abstract

Alcohol and nicotine are two of the oldest and most commonly used recreational drugs, and many people use both of them together. Although their ready availability likely contributes to the strong correlation between alcohol and nicotine use, several lines of evidence suggest that biological factors play a role as well. For example, both alcohol and nicotine act on a brain system called the mesolimbic dopamine system, which mediates the rewarding and reinforcing properties of both drugs. Modification of the activities of the mesolimbic dopamine system can interfere with the effects of both alcohol and nicotine. Another mechanism that may contribute to alcohol-nicotine interactions is cross-tolerance to the effects of both drugs. Finally, genetic studies in humans and of selectively bred mouse and rat strains suggest that shared genetic factors help determine a person's liability to use or abuse both alcohol and nicotine.

Figure 1

Interactive effects of alcohol and nicotine on dopamine release in the rat brain. Under normal conditions, neurons from the pedunculopontine tegmental nucleus (PPT) that release the neurotransmitter acetylcholine (ACh) extend to the ventral tegmental area (VTA). Released ACh (open circles) stimulate nicotinic receptors on neurons that in turn release the neurotransmitter dopamine (DA) in several brain regions, including the nucleus accumbens (NAC). When nicotine (black circles) enters the brain from the circulation, it acts on the nicotinic receptors on the dopamine-containing neurons in the VTA, resulting in increased dopamine release (shaded circles) in the NAC. Alcohol also causes dopamine release in the VTA and NAC through an unknown, but likely indirect, mechanism. The combined effects of alcohol and nicotine can enhance dopamine release in the NAC.

Figure 2

A P rats (closed symbols), which are genetically selected for high alcohol drinking, self-administer more nicotine intravenously than do NP rats (open symbols), which are selected for low drinking. The animals were allowed to self-administer nicotine during the daily 1-hour sessions under different reinforcement schedules^†. The number of nicotine infusions earned by the animals during the first 24 days of nicotine self-administration (0.03 mg/kg per infusion) is shown. B The two strains do not differ in the amount of cocaine they self-administer intravenously. The number of cocaine infusions during the first 14 days of cocaine self-administration (0.75 mg/kg per infusion) is shown. SOURCE: Modified from Le et al., 2006. © 2006, Society for Neuroscience. ^*Days when P rats self-administered significantly more nicotine that NP rats. ^†With the FR-1 schedule, animals had to press a lever once to receive the infusion, with the FR-2 schedule they had to press the lever twice, and with the FR-5 schedule they had to press the lever five times.