Tobacco dependence, the insular cortex and the hypocretin connection

Laboratory of Behavioral and Molecular Neuroscience, Department of Molecular Therapeutics, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.
Pharmacology Biochemistry and Behavior (Impact Factor: 2.78). 02/2011; 97(4):700-7. DOI: 10.1016/j.pbb.2010.08.015
Source: PubMed


Tobacco use is a major cause of disease and premature death in the United States. Nicotine is considered the key component of tobacco responsible for addiction in human smokers. Accumulating evidence supports an important role for the hypocretin (orexin) neuropeptide system in regulating the reinforcing properties of most major drugs of abuse, including nicotine. Here, data showing that nicotine activates hypocretin-producing neurons in the lateral hypothalamus, and that disruption of hypocretin transmission decreases nicotine self-administration behavior in rats will be reviewed. Recent findings suggesting that plasma hypocretin levels may be related to the magnitude of cigarette craving in abstinent smokers will be discussed. Finally, the data suggesting that hypocretin transmission in the insular cortex may play an important role in regulating nicotine self-administration behavior in rats will be reviewed. This latter finding may provide mechanistic insight into the apparent disruption of tobacco addiction reported in human smokers with stroke-associated damage to the insular cortex.

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    • "Since its discovery, studies on orexin have been growing rapidly and made a series of achievements . Many studies have confirmed that the function of orexin neurons was mainly reflected through the regulation of arousal and sleep [3] [4] [5] [6] [7] [8] [9], stimulating feeding [10] [11] [12] [13] [14], regulating drinking behavior [15], and activating the function of adrenal [16] and cardiovascular system [17]. Later investigations on the orexin system have suggested a possible role of orexins in addictive behaviors [18]. "
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    ABSTRACT: This study sought to explore the degree of orexin levels in Chinese opiate and methamphetamine addicts and the differences between them. The cross-sectional study was conducted among detoxified drug addicts from Mandatory Detoxification Center (MDC) in five Chinese cities. Orexin levels were assayed with radioimmunoassay (RIA). Mann-Whitney U test and Kruskal-Wallis test were used to detect differences across groups, and logistic regression was used to explore the association between orexin levels and characteristics of demographic and drug abuse. Between November 2009 and January 2011, 285 opiates addicts, 112 methamphetamine addicts, and 79 healthy controls were enrolled. At drug withdrawal period, both opiate and methamphetamine addicts had lower median orexin levels than controls, and median orexin levels in opiate addicts were higher than those in methamphetamine addicts (all above P < 0.05). Adjusted odds of the above median concentration of orexin were higher for injection than "chasing the dragon" (AOR = 3.1, 95% CI = 1.2-7.9). No significant factors associated with orexin levels of methamphetamine addicts were found. Development of intervention method on orexin system by different administration routes especially for injected opiate addicts at detoxification phase may be significant and was welcome.
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    • "Ultimately, it was established that Hcrtr-1 knockout mice (also trained on a FR5) self-administered far less cocaine than wildtype mice across the entire dose-response function (Hollander et al., 2012). Thus, a plausible explanation is that Hcrt transmission may be necessary to maintain cocaine-taking behavior when high levels of effort are required to obtain the drug, but not when the drug is readily available (Kenny, 2011). "
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    ABSTRACT: A general consensus acknowledges that drug consumption (including alcohol, tobacco, and illicit drugs) constitutes the leading cause of preventable death worldwide. But the global burden of drug abuse extends the mortality statistics. Indeed, the comorbid long-term debilitating effects of the disease also significantly deteriorate the quality of life of individuals suffering from addiction disorders. Despite the large body of evidence delineating the cellular and molecular adaptations induced by chronic drug consumption, the brain mechanisms responsible for drug craving and relapse remain insufficiently understood, and even the most recent developments in the field have not brought significant improvement in the management of drug dependence. Though, recent preclinical evidence suggests that disrupting the hypocretin (orexin) system may serve as an anticraving medication therapy. Here, we discuss how the hypocretins, which orchestrate normal wakefulness, metabolic health and the execution of goal-oriented behaviors, may be compromised and contribute to elicit compulsive drug seeking. We propose an overview on the most recent studies demonstrating an important role for the hypocretin neuropeptide system in the regulation of drug reward and the prevention of drug relapse, and we question the relevance of disrupting the hypocretin system to alleviate symptoms of drug addiction.
    Full-text · Article · Jun 2013 · Frontiers in Behavioral Neuroscience
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    • "Indeed, changes in the prefrontal cortex have recently been found in CH patients [31,32], but dysfunction in prefrontal cortex is also involved in drug addiction [33]. Orexin neuropeptide systems have been suggested to have an important role in both CH pathogenesis [34] and the regulation of the reinforcing properties of most major drugs of abuse [35], including nicotine [36]. A support of this hypothesis is that patients suffering from CH have a greater prevalence of the use of illicit drugs compared to healthy controls [37]. "
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    ABSTRACT: Background The majority of patients suffering from cluster headache (CH) are smokers and it has been suggested that smoking may trigger the development of CH. The aim of this pilot survey was to describe: 1. the differences between current, former, and never smokers CH patients; 2. if smoking changed during an active cluster period; 3. if CH changed after quitting. Methods All outpatients with episodic CH according to the criteria of ICHD-II who were consecutively seen for the first time from October 2010 to April 2012 at a headache centre were interviewed by phone using a specifically prepared questionnaire. Statistical differences between continuous variables were analysed by the Student’s t-test or the one-way analysis of variance (ANOVA), followed by Newman-Keuls post-hoc testing. Comparisons between percentages were made using the Chi-square test or Fisher’s exact test. All data were expressed as the mean ± standard deviation (SD). Results Among a total of 200 patients surveyed (172 males, 28 females; mean age ± SD: 48.41 ± 12 years) there were 60%, 21%, and 19% of current, former, and never smokers, respectively. Current smokers reported longer active periods (12.38 ± 10 weeks) and a higher maximum number of attacks per day (3.38 ± 1) compared to never smoker CH patients (5.68 ± 4 weeks, P <0.05 and 2.47 ± 1, P <0.05, respectively). During the active period most of the patients stated to decrease (45.7%) or not to change (45.7%) the number of cigarettes smoked. Among those who decreased smoking, most (83.8%) reported that they had less desire to smoke. After quitting, the majority of former smokers stated that their headache had not changed. Conclusions Patients with episodic CH who are also smokers appear to have a more severe form of the disorder. However, it is unlikely that between CH and smoking there is a causal relationship, as CH patients rarely improve quitting smoking.
    Full-text · Article · Jun 2013 · The Journal of Headache and Pain
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