Light alcohol intake during adolescence induces alcohol addiction in a neurodevelopmental model of schizophrenia

Jeanblanc, Jérôme; Balguerie, Kevin; Coune, F.; Legastelois, Rémi; Jeanblanc, Virginie; Naassila, Mickaël

doi:10.1111/adb.12146

Cited by 37 publications

(38 citation statements)

References 49 publications

(61 reference statements)

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“…While the hamster serves as a useful bioassay for assessing the effects of antipsychotics on alcohol drinking in patients with SCZ, it is not an animal model of SCZ. Thus, future studies will need to draw upon such an animal model (e.g., the neonatal ventral hippocampal lesioned rat; Jeanblanc et al, 2014), and on techniques such as magnetic resonance spectroscopy and microdialysis to assess neurotransmitter functioning. Both directions of research are required to better understand the mechanism by which CLOZ or CLOZ-like drugs reduce alcohol drinking in animals, in patients with SCZ, and potentially, in those with AUD alone.…”

Section: Discussionmentioning

confidence: 99%

Clozapine reconstructed: Haloperidol's ability to reduce alcohol intake in the Syrian golden hamster can be enhanced through noradrenergic modulation by desipramine and idazoxan

Khokhar

Chau

Dawson

et al. 2015

Drug and Alcohol Dependence

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Background Alcohol use disorder commonly occurs in patients with schizophrenia. Most antipsychotic drugs do not lessen alcohol use; although the atypical antipsychotic clozapine has been shown to reduce alcohol use in patients with schizophrenia, its toxicity severely limits its use in patients. With an eye toward creation of a safer clozapine-like drug, we have investigated the pharmacological basis of the clozapine’s effects on alcohol drinking in the Syrian golden hamster. In this animal, as in patients with schizophrenia, clozapine reduces alcohol drinking while the typical antipsychotic haloperidol does not. We have suggested that clozapine decreases alcohol drinking due to its weak dopamine D2 receptor blockade, its potent norepinephrine α-2 receptor antagonism, as well as its ability to elevate plasma norepinephrine. Methods We recreated a clozapine-like drug to reduce alcohol drinking in the Syrian golden hamster by combining low dose haloperidol with a norepinephrine α-2 receptor antagonist, idazoxan, and a norepinephrine reuptake inhibitor, desipramine. Hamsters were given free access to water and alcohol (15% v/v) and were treated daily with each drug or with the three-drug combination for 23 days. Results The drug combination reduced alcohol drinking and preference significantly as compared to vehicle or to haloperidol, idazoxan or desipramine, while not altering food-intake or bodyweight. Conclusion These findings suggest that that haloperidol, which does not reduce alcohol drinking in patients with schizophrenia or the hamster, if combined with idazoxan and desipramine (producing a drug combination that mimics aspects of clozapine’s pharmacology) is able to reduce alcohol drinking in the hamster.

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Section: Discussionmentioning

confidence: 99%

Clozapine reconstructed: Haloperidol's ability to reduce alcohol intake in the Syrian golden hamster can be enhanced through noradrenergic modulation by desipramine and idazoxan

Khokhar

Chau

Dawson

et al. 2015

Drug and Alcohol Dependence

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“…Studies using animal models have also indicated that voluntary ethanol drinking during adolescence can, in some models, be shown to facilitate the acquisition of alcohol self-administration, increase craving behavior, and/or increase the probability of relapse in those animals in adulthood (see Alaux-Cantin et al, 2013; Gilpin, Karanikas & Richardson, 2012; Jeanblanc et al, 2015; McBride et al, 2005; Serlin & Torregrossa, 2015; Spear, 2000a; Toalston et al, 2015). However, other studies have shown that ethanol exposure during adolescence has no effect on subsequent ethanol consumption in adulthood (Slawecki & Betancourt, 2002).…”

Section: Introductionmentioning

confidence: 99%

Alcohol drinking during adolescence increases consumptive responses to alcohol in adulthood in Wistar rats

Amodeo

Kneiber

Wills

et al. 2017

Alcohol

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Binge drinking and the onset of alcohol use disorders usually peak during the transition between late adolescence and early adulthood, and early adolescent onset of alcohol consumption has been demonstrated to increase the risk for alcohol dependence in adulthood. In the present study we describe an animal model of early adolescent alcohol consumption where animals drink unsweetened and unflavored ethanol in high concentrations (20%). Using this model we investigated the influence of drinking on alcohol-related appetitive behavior and alcohol consumption levels in early adulthood. Further, we also sought to investigate whether differences in alcohol-related drinking behaviors were specific to exposure in adolescence versus exposure in adulthood. Male Wistar rats were given a 2-bottle choice between 20% ethanol and water in one group and between two water bottles in another group during their adolescence (Postnatal Day (PD) PD26-59) to model voluntary drinking in adolescent humans. As young adults (PD85), rats were trained in a paradigm that provided free access to 20% alcohol for 25 min after completing up to a fixed ratio (FR) 16-lever press response. A set of young adult male Wistar rats was exposed to the same paradigm using the same time course beginning at PD92. The results indicate that adolescent exposure to alcohol increased consumption of alcohol in adulthood. Furthermore, when investigating differences between adolescent high and low adolescent drinkers in adulthood, high consumers continued to drink more alcohol, had fewer FR failures, and had faster completion of FR schedules in adulthood whereas the low consumers were no different than controls. Rats exposed to ethanol in young adulthood also increased future intake but there were no differences in any other components of drinking behavior. Both adolescent- and adult-exposed rats did not exhibit an increase in lever pressing during the appetitive challenge session. These data indicate that adolescent and early adult alcohol exposure can increase consumptive aspects of drinking but that adolescent exposure may preferentially influence the motivation to drink.

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“…Chambers' group has largely investigated the adult consumption of drugs of abuse such as cocaine [77,78], nicotine [79,80], and also alcohol [81,82] with this model showing increased consumption of the different drugs of abuse at adulthood. However, our group was the first to investigate the impact of adolescent alcohol exposure on subsequent AUDs in adulthood in the NVHL model of schizophrenia [83]. In this study, we found that moderate alcohol consumption using a 10 % continuous access two-bottle choice paradigm during adolescence (postnatal days 28 to 42) is necessary to observe at adulthood a loss of control over alcohol consumption.…”

Section: Schizophreniamentioning

confidence: 85%

Comorbidity Between Psychiatric Diseases and Alcohol Use Disorders: Impact of Adolescent Alcohol Consumption

Jeanblanc

2015

Curr Addict Rep

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Patients suffering from psychiatric disorders such as schizophrenia and bipolar disorders often suffer from alcohol abuse or dependence. Conversely, most alcoholdependent patients suffer from other psychiatric disorders including depressive or anxiety disorders, with increased risk of suicide ideation and attempts. Adolescence is a crucial period of brain maturation but also of vulnerability to alcohol use disorders and other psychiatric diseases. While global alcohol consumption is decreasing in numerous Western countries, adolescent drinking is increasing with specific patterns of drinking called Bbinge drinking^leading to massive intoxication in a short period of time. Clinical and preclinical studies investigating the relationship between adolescent alcohol consumption and subsequent psychiatric disorders in patients or in animal models of psychiatric disorders will be described here and discussed.

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Light alcohol intake during adolescence induces alcohol addiction in a neurodevelopmental model of schizophrenia

Cited by 37 publications

References 49 publications

Clozapine reconstructed: Haloperidol's ability to reduce alcohol intake in the Syrian golden hamster can be enhanced through noradrenergic modulation by desipramine and idazoxan

Clozapine reconstructed: Haloperidol's ability to reduce alcohol intake in the Syrian golden hamster can be enhanced through noradrenergic modulation by desipramine and idazoxan

Alcohol drinking during adolescence increases consumptive responses to alcohol in adulthood in Wistar rats

Comorbidity Between Psychiatric Diseases and Alcohol Use Disorders: Impact of Adolescent Alcohol Consumption

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