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The brain is an organ of communication. There is no single pathway for any neurobehavioral function or dysfunction. Drug abuse and addiction may at first appear to be due to the particular action of a drug at a neurotransmitter receptor or other physiological target process, but because of the intricate communication among neural systems, actions at a particular receptor quickly involves a much broader array of interacting systems. Thus, nicotine effects on nicotinic receptors and opiate effects on opioid receptors quickly involve directly and indirectly many other neural (and glial) systems involved in drug abuse and addiction. With drug reinforcement the involvement of dopaminergic innervation of the nucleus accumbens is the most obviously important interacting neural system, but there are many other interacting systems that play important roles. This can complicate understanding of the neurobehavioral bases of drug addiction, but it also presents many opportunities for developing effective therapeutic treatments. By investigating these interactions can provide a more accurate understanding of neural bases of addiction and open multiple new opportunities for therapeutic treatment to reduce addiction. This talk will present the series of studies we have conducted with the rat drug self-administration model investigating drug interactions to elucidate nicotinic as well other drugs of abuse.