Molecular and Cellular Aspects of Nicotine Abuse
Salk Institute, لا هویا, California, United StatesNeuron (Impact Factor: 15.05). 06/1996; 16(5):905-8. DOI: 10.1016/S0896-6273(00)80112-9
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- "While the enhancing effects of acute nicotine are well documented, several studies have shown that while chronic nicotine has no effect on fear conditioning , withdrawal from chronic nicotine impairs contextual and trace fear conditioning (André, Gulick, Portugal, & Gould, 2008; Davis, James, Siegel, & Gould, 2005; Portugal & Gould, 2009; Portugal, Wilkinson, Kenney, Sullivan, & Gould, 2012; Raybuck & Gould, 2009). There is also evidence suggesting that during chronic nicotine administration, hippocampal nAChRs desensitize and upregulate and the resulting hypersensitive cholinergic system may be responsible for the effects of nicotine withdrawal on hippocampus-dependent learning (Dani & Heinemann, 1996; Gould et al., 2012; Marks, Grady, & Collins, 1993; Wilkinson & Gould, 2013 ). In sup- port, Gould et al. (2012) found that chronic nicotine increased nAChR binding in the hippocampus and the duration of nAChR upregulation paralleled the duration of withdrawal deficits in hippocampus-dependent learning. "
ABSTRACT: Even though smoking rates have long been on the decline, nicotine addiction still affects 20% of the US population today. Moreover, nicotine dependence shows high comorbidity with many mental illnesses including, but are not limited to, attention deficit hyperactivity disorder, anxiety disorders, and depression. The reason for the high rates of smoking in patients with mental illnesses may relate to attempts to self-medicate with nicotine. While nicotine may alleviate the symptoms of mental disorders, nicotine abstinence has been shown to worsen the symptoms of these disorders. In this chapter, we review the studies from animal and human research examining the bidirectional relationship between nicotine and attention deficit hyperactivity disorder, anxiety disorders, and depression as well as studies examining the roles of specific subunits of nicotinic acetylcholine receptors (nAChRs) in the interaction between nicotine and these mental illnesses. The results of these studies suggest that activation, desensitization, and upregulation of nAChRs modulate the effects of nicotine on mental illnesses.
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- ". Therefore, it is suggested that in the absence of nicotine during withdrawal, upregulated nAChRs re-sensitize, which results in a hypersensitive cholinergic system and deficits in hippocampus-dependent learning . This hypothesis was supported by Gould et al.'s  "
ABSTRACT: Anxiety disorders are a group of crippling mental diseases affecting millions of Americans with a 30% lifetime prevalence and costs associated with healthcare of $42.3 billion. While anxiety disorders show high levels of co-morbidity with smoking (45.3% vs. 22.5% in healthy individuals), anxiety disorders are also more common among the smoking population (22% vs. 11.1% in the non-smoking population). Moreover, there is clear evidence that smoking modulates symptom severity in patients with anxiety disorders. In order to better understand this relationship, several animal paradigms are used to model several key symptoms of anxiety disorders; these include fear conditioning and measures of anxiety. Studies clearly demonstrate that nicotine mediates acquisition and extinction of fear as well as anxiety through the modulation of specific subtypes of nicotinic acetylcholine receptors (nAChRs) in brain regions involved in emotion processing such as the hippocampus. However, the direction of nicotine's effects on these behaviors is determined by several factors that include the length of administration, hippocampus-dependency of the fear learning task, and source of anxiety (novelty-driven vs. social anxiety). Overall, the studies reviewed here suggest that nicotine alters behaviors related to fear and anxiety and that nicotine contributes to the development, maintenance, and reoccurrence of anxiety disorders. Copyright © 2015. Published by Elsevier Inc.
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- "Our current understanding of the mechanisms underlying nicotine-induced excitation of VTA DA neurons is based on studies done using brain slices (Dani and Heinemann, 1996, Mansvelder and McGehee, 2000, Mansvelder et al., 2002). Since the interaction between the VTA and other brain regions is interrupted in brain slices, studies in a more intact in vivo system are needed. "
ABSTRACT: Systemic administration of nicotine increases dopaminergic (DA) neuron firing in the ventral tegmental area (VTA), which is thought to underlie nicotine reward. Here, we report that the medial prefrontal cortex (mPFC) plays a critical role in nicotine-induced excitation of VTA DA neurons. In chloral hydrate-anesthetized rats, extracellular single-unit recordings showed that VTA DA neurons exhibited two types of firing responses to systemic nicotine. After nicotine injection, the neurons with type-I response showed a biphasic early inhibition and later excitation, whereas the neurons with type-II response showed a monophasic excitation. The neurons with type-I, but not type-II, response exhibited pronounced slow oscillations (SOs) in firing. Pharmacological or structural mPFC inactivation abolished SOs and prevented systemic nicotine-induced excitation in the neurons with type-I, but not type-II, response, suggesting that these VTA DA neurons are functionally coupled to the mPFC and nicotine increases firing rate in these neurons in part through the mPFC. Systemic nicotine also increased the firing rate and SOs in mPFC pyramidal neurons. mPFC infusion of a non-α7 nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine blocked the excitatory effect of systemic nicotine on the VTA DA neurons with type-I response, but mPFC infusion of nicotine failed to excite these neurons. These results suggest that nAChR activation in the mPFC is necessary, but not sufficient, for systemic nicotine-induced excitation of VTA neurons. Finally, systemic injection of bicuculline prevented nicotine-induced firing alterations in the neurons with type-I response. We propose that the mPFC plays a critical role in systemic nicotine-induced excitation of VTA DA neurons.