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

Abstract

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.

Combined Active and Passive Immunization Enhances the Efficacy of Immunotherapy against Nicotine in Rats

“…Previous studies have reported attenuation of acute nicotine-induced locomotor activity (as distinct from sensitization) after passive immunization with a polyclonal anti-nicotine antiserum (Pentel et al, 2000), and vaccination or passive immunization with a monoclonal antibody (Carrera et al, 2004). The current study extends these data to LMS, a behavior mediated by pathways that overlap substantially with those mediating drug reinforcement and that is relevant to addiction treatment (DiFranza and Wellman, 2007). The data show that both vaccination alone and passive immunization alone are effective in attenuating LMS to nicotine, and they suggest that the pharmacokinetic and behavioral effects of immunotherapy depend on the total antibody concentration rather than their source (endogenously produced after vaccination or passively administered).…”

Chronic nicotine attenuates behavioral and synaptic plasticity impairments in a streptozotocin model of Alzheimer’s disease

“…The agonism of a7 and a4b2 nAChR subtypes can be among the Nic-mediated changes we observed here. In fact, chronic Nic exposure may trigger a cascade of events involving nicotinic receptor desensitization followed by long-lasting up-regulation (Gould and Leach, 2014;Markou, 2008;Dani and Bertrand, 2007;DiFranza and Wellman, 2007). We suggest that these processes could compensate for the disrupted cholinergic transmis- sion in icv-STZ, thus ameliorating mnemonic and synaptic plasticity deficits.…”

State of the Science

“…86 The rationale behind smoking cessation in HF is that nicotine has vasoconstrictor and proinflammatory activity. 87,88 Smoking cessation has been shown to reduce adverse outcomes and decrease mortality in HF, 89 yet a surprising number of people with HF continue to smoke. In a recent survey of 3778 German adults with a smoking history, more than half (52%) of those with a circulatory disorder, including HF, were current smokers.…”