Intense Sweetness Surpasses Cocaine Reward

BACKGROUND: Refined sugars (e.g., sucrose, fructose) were absent in the diet of most people until very recently in human history. Today overconsumption of diets rich in sugars contributes together with other factors to drive the current obesity epidemic. Overconsumption of sugar-dense foods or beverages is initially motivated by the pleasure of sweet taste and is often compared to drug addiction. Though there are many biological commonalities between sweetened diets and drugs of abuse, the addictive potential of the former relative to the latter is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that when rats were allowed to choose mutually-exclusively between water sweetened with saccharin-an intense calorie-free sweetener-and intravenous cocaine-a highly addictive and harmful substance-the large majority of animals (94%) preferred the sweet taste of saccharin. The preference for saccharin was not attributable to its unnatural ability to induce sweetness without calories because the same preference was also observed with sucrose, a natural sugar. Finally, the preference for saccharin was not surmountable by increasing doses of cocaine and was observed despite either cocaine intoxication, sensitization or intake escalation-the latter being a hallmark of drug addiction. CONCLUSIONS: Our findings clearly demonstrate that intense sweetness can surpass cocaine reward, even in drug-sensitized and -addicted individuals. We speculate that the addictive potential of intense sweetness results from an inborn hypersensitivity to sweet tastants. In most mammals, including rats and humans, sweet receptors evolved in ancestral environments poor in sugars and are thus not adapted to high concentrations of sweet tastants. The supranormal stimulation of these receptors by sugar-rich diets, such as those now widely available in modern societies, would generate a supranormal reward signal in the brain, with the potential to override self-control mechanisms and thus to lead to addiction

Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction

International audienceBACKGROUND:Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought.METHODOLOGY/PRINCIPAL FINDINGS:Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories.CONCLUSIONS/SIGNIFICANCE:This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development

Qu’apporte la neurobiologie aux addictions ?

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Heroin Addiction: Anticipating the Reward of Heroin or the Agony of Withdrawal?

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Caractérisation d'un modèle animal d'addiction (de la compulsion au choix)

Les addictions aux drogues sont définies comme des consommations compulsives de toxiques, c'est-à-dire excessives et difficiles à contrôler, et ce malgré les conséquences néfastes associées. Un des grands enjeux de la recherche dans le domaine des addictions est de comprendre et d'expliquer comment les individus passent d'un mode de consommation contrôlé à un mode de consommation compulsif de toxique. Récemment, un modèle de la transition entre l'usage et l'addiction à la cocaine a été développé et validé partiellement chez le rat. Le but de mon travail de thèse a été de poursuivre la validation de ce modèle. Plus précisément, mon travail a eu pour objectifs : 1) d'achever la validation du modèle avec la cocaine, 2) de généraliser la validation du modèle à une autre substance addictive, l'héroine, et enfin 3) d'étudier l'existence de mécanismes communs aux consommations compulsives de cocaine et d'héroine. Nos principaux résultats démontrent que quelle que soit la drogue, la majorité des sujets développe la plupart des signes comportementaux de l'addiction après un accès prolongé à la drogue. Cependant, contre toute attente, les animaux exposés longuement à la drogue ne présentent pas un désintérêt progressif vis-à-vis des récompenses alternatives. En fait, face à un choix, la majorité préfère la sensation naturelle d'un édulcorant (saccharine, sucrose) aux sensations artificielles de la drogue. Cette découverte inattendue pourrait conduire : i) à une reformulation des théories neurobiologiques actuelles de l'addiction, ii) à une remise en cause du postulat de la continuité animal-homme dans l'addiction et/ou, iii) à une nouvelle hiérarchisation des stimuli addictifs.Drug addiction is defined as compulsive drug use - that is, excessive and difficult to control despite negative consequences. A critical problem in current addiction research is to understand the transition between controlled and compulsive drug use. A rat model of the transition to cocaine addiction was recently developed and partially validated. The goal of my thesis was to continue the validation of this model. My specific aims were : 1) to finish the validation of the model with cocaine, 2) to generalize the validation of the model to heroin, 3) to study the potential existence of common mechanisms underlying cocaine and heroin compulsive consumption. Our main results demonstrated that regardless of the tested drug (cocaine or heroin), most individuals with prolonged drug exposure developed most of the behavioral signs of addiction. Surprisingly, however, rats did not show a progressive neglect of alternative rewards after a prolonged access to the drug. In fact, when they had the choice, rats preferred an intense sensation of sweetness (saccharin or sucrose) to an artificial stimulation of drug. The unexpected discovery that intense sweetness surpasses drug reward may lead to : i) a reformulation of current neurobiological theories of addiction ii) a reappraisal of the postulate of a continuity between animals and humans in addiction vulnerability and/or iii) a re-ordering in the hierarchy of potentially addictive stimuli.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Intravenous nicotine injection induces rapid, experience-dependent sensitization of glutamate release in the ventral tegmental area and nucleus accumbens

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Heroin-Induced Reinstatement is Specific to Compulsive Heroin Use and Dissociable from Heroin Reward and Sensitization

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Heroin-Induced Reinstatement is Specific to Compulsive Heroin Use and Dissociable from Heroin Reward and Sensitization

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The opioid receptors as targets for drug abuse medication

International audienceThe endogenous opioid system is largely expressed in the brain, and both endogenous opioid peptides and receptors are present in areas associated with reward and motivation. It is well known that this endogenous system plays a key role in many aspects of addictive behaviours. The present review summarizes the modifications of the opioid system induced by chronic treatment with drugs of abuse reported in preclinical and clinical studies, as well as the action of opioid antagonists and agonists on the reinforcing effects of drugs of abuse, with therapeutic perspectives. We have focused on the effects of chronic psychostimulants, alcohol and nicotine exposure. Taken together, the changes in both opioid peptides and opioid receptors in different brain structures following acute or chronic exposure to these drugs of abuse clearly identify the opioid system as a potential target for the development of effective pharmacotherapy for the treatment of addiction and the prevention of relapse