Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse

Abstract

Concurrent use of tobacco and alcohol or psychostimulants represents a major public health concern, with use of one substance influencing consumption of the other. Co-abuse of these drugs leads to substantial negative health outcomes, reduced cessation, and high economic costs, but the underlying mechanisms are poorly understood. Epidemiological data suggest that tobacco use during adolescence plays a particularly significant role. Adolescence is a sensitive period of development marked by major neurobiological maturation of brain regions critical for reward processing, learning and memory, and executive function. Nicotine exposure during this time produces a unique and long-lasting vulnerability to subsequent substance use, likely via actions at cholinergic, dopaminergic, and serotonergic systems. In this review, we discuss recent clinical and preclinical data examining the genetic factors and mechanisms underlying co-use of nicotine and alcohol or cocaine and amphetamines. We evaluate the critical role of nicotinic acetylcholine receptors throughout, and emphasize the dearth of preclinical studies assessing concurrent drug exposure. We stress important age and sex differences in drug responses, and highlight a brief, low-dose nicotine exposure paradigm that may better model early use of tobacco products. The escalating use of e-cigarettes among youth necessitates a closer look at the consequences of early adolescent nicotine exposure on subsequent alcohol and drug abuse.

Keywords: Adolescence; amphetamine; co-dependence; cocaine; e-cigarettes; ethanol; nicotinic acetylcholine receptors; tobacco.

Figure 1

Overlapping receptor systems involved in nicotine and alcohol or psychostimulant dependence. Genetic and pharmacological studies in both humans and rodents suggest that co-use of nicotine and alcohol or psychostimulants is mediated, in part, by activity at overlapping substrates. In particular, cholinergic and serotonergic systems underlie reward-related behaviors, including drug intake, preference, and dependence to all three drugs of abuse. Asterisks (*) indicate nAChRs containing other subunits. Italics indicate human genes. KOR = kappa opioid receptor.