Sensitization to nicotine: how the animal literature might inform future human research

Despite a rich neuroscience literature on sensitization, this phenomenon has been neglected in clinical nicotine research. This paper offers a primer on the neuroscience of nicotine sensitization for behavioral scientists, identifying key concepts, potential theoretical and clinical implications, and directions for future research. Sensitization to a drug occurs when repeated exposures to the same dose produce greater responses. In animals, sensitization to nicotine, morphine, alcohol, cocaine, amphetamine, and methamphetamine manifests as increased locomotor activity. In animals, sensitization to nicotine begins with the first dose and is maximal within 5-7 days. It involves multiple neurotransmitters, receptors, and brain structures and cannot be attributed to any single alteration. The processes involved in its induction and expression are not identical. The neurologic changes associated with sensitization are not consistent across drugs, suggesting that sensitization is not an accident of neurophysiology but perhaps an exaggerated adaptive response. Sensitization is incorporated into two theories of addiction: incentive-sensitization and sensitization-homeostasis. Whether sensitization occurs in humans and how it is expressed is unclear, as is its role in human addiction.