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Molecular and Cellular Aspects of Nicotine Abuse

Salk Institute, لا هویا, California, United States
Neuron (Impact Factor: 15.98). 06/1996; 16(5):905-8. DOI: 10.1016/S0896-6273(00)80112-9
Source: PubMed
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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. "
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    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.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 09/2012; 32(36):12366-12375. DOI:10.1523/JNEUROSCI.5411-11.2012 · 6.75 Impact Factor
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    • "Based on current results and prior studies, a model of a potential underlying mechanism of nicotine withdrawal-related deficits in hippocampus-dependent learning can be put forth. This model is extrapolated from an earlier model proposed by Dani and Heinemann (1996) in which during periods of low nicotine levels, upregulated nAChRs would be excessively responsive to ACh. "
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    ABSTRACT: A predominant symptom of nicotine withdrawal is cognitive deficits, yet understanding of the neural basis for these deficits is limited. Withdrawal from chronic nicotine disrupts contextual learning in mice and this deficit is mediated by direct effects of nicotine in the hippocampus. Chronic nicotine treatment upregulates nicotinic acetylcholine receptors (nAChR); however, it is unknown whether upregulation is related to the observed withdrawal-induced cognitive deficits. If a relationship between altered learning and nAChR levels exists, changes in nAChR levels after cessation of nicotine treatment should match the duration of learning deficits. To test this hypothesis, mice were chronically administered 6.3mg/kg/day (freebase) nicotine for 12 days and trained in contextual fear conditioning on day 11 or between 1 to 16 days after withdrawal of treatment. Changes in [(125)I]-epibatidine binding at cytisine-sensitive and cytisine-resistant nAChRs and chronic nicotine-related changes in α4, α7, and β2 nAChR subunit mRNA expression were assessed. Chronic nicotine had no behavioral effect but withdrawal produced deficits in contextual fear conditioning that lasted 4 days. Nicotine withdrawal did not disrupt cued fear conditioning. Chronic nicotine upregulated hippocampal cytisine-sensitive nAChR binding; upregulation continued after cessation of nicotine administration and the duration of upregulation during withdrawal paralleled the duration of behavioral changes. Changes in binding in cortex and cerebellum did not match behavioral changes. No changes in α4, α7, and β2 subunit mRNA expression were seen with chronic nicotine. Thus, nicotine withdrawal-related deficits in contextual learning are time-limited changes that are associated with temporal changes in upregulation of high-affinity nAChR binding.
    Neuropharmacology 04/2012; 62(5-6):2118-25. DOI:10.1016/j.neuropharm.2012.01.003 · 4.82 Impact Factor
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    • "Nicotine [1-methyl-2-(3-pyridyl-pyrrolidine), C 10 H 14 N 2 ] is the principal component of tobacco [1]. The predominant effects of nicotine include rise in blood pressure, heart rate, respiratory rate; increase in the level of catecholamines in blood; increase in level of free fatty acids, mobilization of blood sugar, and it was also found to disturb the antioxidant defense mechanisms [2] [3] [4] [5] [6]. There is strong evidence that smokeless tobacco use leads to oral mucosal lesions [7] [8] including oral pre-cancerous lesions, gingival recession [9], cardiovascular risk factors and disease, diabetes, reproductive health effects, and overall mortality. "
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    ABSTRACT: The use of tobacco products as dentifrices is still prevalent in various parts of India. Tobacco use in dentifrices is a terrible scourge which motivates continued use despite its harmful effects. Indian legislation prohibits the use of nicotine in dentifrices. Nicotine is primarily injurious to people because it is responsible for tobacco addiction and is dependence forming. The present study was motivated by an interest in examining the presence of nicotine in these dentifrices. Our earlier report indicates the presence of nicotine in toothpowders. To further curb the menace of tobacco, our team again analysed the toothpowder brands of previous years and in toothpastes as well. Eight brands of commonly used toothpastes and toothpowders were evaluated by gas chromatography-mass spectroscopy. On the whole, there are a few successes but much remains to be done. Our findings indicated the presence of nicotine in two brands of dant manjans and four brands of toothpastes. Further our finding underscores the need for stringent regulations by the regulatory authorities for preventing the addition of nicotine in these dentifrices. Hence government policy needs to be targeted towards an effective control of tobacco in these dentifrices and should be properly addressed.
    Journal of Toxicology 01/2012; 2012:237506. DOI:10.1155/2012/237506
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