• Energy Research

Schizophrenia is a mental disorder characterized by a series of positive, negative or cognitive symptoms but with also the particularity of exhibiting a high rate of co-morbid use of drugs of abuse. While more than 80% of schizophrenics are smokers, the second most consumed drug is alcohol, with dramatic consequences on frequency and intensity of psychotic episodes and on life expectancy. Here we investigated the impact of light alcohol intake during adolescence on the subsequent occurrence of alcohol addiction-like behavior in neonatal ventral hippocampal lesion (NVHL) rats, a neurodevelopmental model of schizophrenia. Our findings demonstrated an increased liability to addictive behaviors in adult NVHL rats after voluntary alcohol intake during adolescence. NVHL rats displayed several signs of alcohol use disorder such as a loss of control over alcohol intake and high motivation to consume alcohol, associated with a higher resistance to extinction. In addition, once NVHL rats relapsed, they maintained higher drinking levels than controls. We finally showed that the anti-addictive drug naltrexone is efficient in reducing excessive alcohol intake in NVHL rats. Our results are in accordance with epidemiological studies underlying the particular vulnerability to alcohol addiction after adolescent exposure to alcohol and highlight the fact that schizophrenic subjects may be particularly at risk even after light alcohol consumption. Based on these results, it seems particularly relevant to prevent early onset of alcohol use in at-risk subjects and thus to reduce the incidence of co-morbid alcohol abuse in psychotic patients.

Les pathologies cardiovasculaires sont la deuxième cause de mortalité attribuable à l’alcool, après les cancers. L’impact de la consommation d’alcool sur la pression artérielle et le risque de pathologies cardiovasculaires semble encore largement sous-estimé dans la population générale et par les professionnels de santé. Pourtant, de très nombreuses études ont démontré l’augmentation de la pression artérielle, dose-dépendante, même à des niveaux de consommation proches des repères de consommation (deux verres, soit 20 g/j). Les effets prétendument protecteurs des faibles niveaux de consommation ne sont pas confirmés, même chez les femmes. Le profil de consommation de type « binge drinking » a un impact particulièrement important sur la pression artérielle. L’augmentation de la pression artérielle due à l’alcool est réversible après diminution de la consommation. Plusieurs mécanismes physiopathologiques ont été proposés pour expliquer les effets hypertenseurs de l’alcool. Le repérage de la consommation d’alcool par les professionnels de santé reste largement insuffisant, notamment en France, même chez les sujets hypertendus alors qu’une intervention est efficace. Il apparaît particulièrement important de renforcer la formation des professionnels de santé et le repérage de la consommation d’alcool à des fins de prévention primaire mais aussi secondaire lorsque l’hypertension est déjà installée. Les sociétés savantes et fédérations devraient renforcer la communication sur les risques liés à la consommation d’alcool. Cardiovascular disease is the second leading cause of alcohol-attributable mortality after cancer. The impact of alcohol consumption on blood pressure and the risk of cardiovascular pathologies are still largely underestimated by the general population and health professionals. However, numerous studies have demonstrated a dose-dependent increase in blood pressure, even at consumption levels close to the consumption guidelines (two drinks i.e. 20g per day). The alleged protective effects of low consumption levels are not confirmed, even in women. The binge drinking pattern has a particularly strong impact on blood pressure. The increase in blood pressure due to alcohol is reversible after reduction of consumption. Several pathophysiological mechanisms have been proposed to explain the hypertensive effects of alcohol. The screening of alcohol consumption by health professionals remains largely insufficient, especially in France, even in hypertensive subjects, although intervention is effective. It seems particularly important to reinforce the training of health professionals and the screening of alcohol consumption for primary prevention and also for secondary prevention when hypertension is already established. Scientific societies and federations should reinforce communication on the risks associated with alcohol consumption.

Several works have suggested a potential role for nitric oxide in alcohol-seeking behavior and we have recently shown that the specific blockade of the expression of the neuronal nitric oxide synthase (NOS1) decreases rat ethanol intake. Our previous results have also shown that chronic ethanol exposure has differential effect on the brain NOS activity depending on rat brain area. In the present study, we examine the effects of chronic administration of ethanol on the NOS1-mRNA levels measured with the competitive reverse transcriptase-polymerase chain reaction technique. Chronic administration of ethanol differentially regulated NOS1-mRNA levels depending on rat brain area. Chronic ethanol exposure had no effect on the NOS1-mRNA levels in frontal cortex, but decreased the NOS1-mRNA levels in hippocampus (P<0.01, 39% decrease) and induced a strong increase in striatum (P<0.01, 92% increase). These effects of ethanol were not affected by 7-nitro indazole (25 mg/kg, i.p. daily for 1 week) treatment. These data further support that NOS1 is regulated by chronic exposure to ethanol and that these effects are related to modifications of mRNA levels.

BackgroundData have shown a role of α‐synuclein in anxiety and also in addiction, particularly in alcohol use disorders (AUD). Since the comorbidity between AUD and anxiety is very high and because anxiety is an important factor in ethanol (EtOH) relapse, the aim of the present study was to investigate the role of α‐synuclein in moderating EtOH intake, the anxiolytic effects of EtOH, and EtOH withdrawal–induced anxiety and convulsions in mice. The study aimed to determine whether SNCA variants moderated anxiety in EtOH‐dependent patients.MethodsWe analyzed the moderator effect of 3 SNCA Tag‐single nucleotide polymorphisms (Tag‐SNPs) rs356200, rs356219, and rs2119787 on the anxiety symptoms in 128 EtOH‐dependent patients. We used the C57BL/6JOlaHsd Snca mutant mice to assess EtOH intake; sensitivity to the anxiolytic effects of EtOH in a test battery comprising the open field, the light–dark box, and the elevated plus maze; and both anxiety and convulsions induced by EtOH withdrawal.ResultsOur results demonstrated a reduction in both EtOH intake and preference and also a lack of sensitivity to the anxiolytic effects of EtOH in α‐synuclein mutant mice. Results on anxiety‐like behavior were mixed, but mutant mice displayed increased anxiety when exposed to a low anxiogenic environment. Mutant mice also displayed an increase in handling‐induced convulsion scores during withdrawal after EtOH inhalation, but did not differ in terms of EtOH withdrawal–induced anxiety. In humans, we found a significant association of the rs356219 SNP with a high level of anxiety (Beck Anxiety Inventory score >15) and the rs356200 SNP with a positive familial history of AUD.ConclusionsOur translational study highlights a significant role of α‐synuclein in components of AUD.

AbstractRationaleBinge drinking (BD), characterized by recurring alternations between intense intoxication episodes and abstinence periods, is the most frequent alcohol consumption pattern in youth and is growing in prevalence among older adults. Many studies have underlined the specific harmful impact of this habit by showing impaired abilities in a wide range of cognitive functions among binge drinkers, as well as modifications of brain structure and function.AimsSeveral controversies and inconsistencies currently hamper the harmonious development of the field and the recognition of BD as a specific alcohol consumption pattern. The main concern is the absence of consensual BD conceptualization, leading to variability in experimental group selection and alcohol consumption evaluation. The present paper aims at overcoming this key issue through a two-step approach.Methods and conclusionsFirst, a literature review allows proposing an integrated BD conceptualization, distinguishing it from other subclinical alcohol consumption patterns. Six specific characteristics of BD are identified, namely, (1) the presence of physiological symptoms related to BD episodes, (2) the presence of psychological symptoms related to BD episodes, (3) the ratio of BD episodes compared to all alcohol drinking occasions, (4) the frequency of BD episodes, (5) the consumption speed and (6) the alternation between BD episodes and soberness periods. Second, capitalizing on this conceptual clarification, we propose an evaluation protocol jointly measuring these six BD characteristics. Finally, several research perspectives are presented to refine the proposed conceptualization.

Chronic ethanol exposure during the fetal period alters spontaneous neuronal discharge, excitatory and inhibitory amino acid neurotransmission and neuronal sensitivity to ethanol in the adult brain. However, nothing is known about the effects of such exposure on the central respiratory rhythmic network, which is highly dependent on ethanol‐sensitive amino acid neurotransmission. In 3‐ to 4‐week‐old rats, we investigated (1) the effects of chronic ethanol exposure (10% v/v as only source of fluid) during gestation and lactation on phrenic (Phr) and hypoglossal (XII) nerve activity using anin situpreparation and on spontaneous breathing at rest in unanaesthetized animals using plethysmography; (2) the sensitivity of the respiratory system to ethanol re‐exposurein situ; and (3) the phrenic nerve response to muscimol, a GABAAreceptor agonist, applied systemically in anin situpreparation. In control rats, ethanol (10–80 mm) induced a concentration‐dependent decrease in the amplitude of both XII and Phr motor outflows. At 80 mmethanol, the amplitude of the activity of the two nerves displayed a difference in sensitivity to ethanol and respiratory frequency increased as a result of shortening of postinspiratory duration period. After chronic ethanol exposure, respiratory frequency was significantly reduced by 43%in situand by 23% in unanaesthetized animals, as a result of a selective increase in expiratory duration. During Phr burst, the ramp was steeper, revealing modification of inspiratory patterning. Interestingly that re‐exposure to ethanolin situelicited a dramatic inhibitory effect. At 80 mm, ethanol abolished rhythmic XII nerve outflow in all cases and Phr nerve outflow in only 50% of cases. Furthermore, administration of 50 µmmuscimol abolished Phr nerve activity in all control rats, but only in 50% of ethanol‐exposed animals. Our results demonstrate that chronic ethanol exposure at an early stage of brain development depresses breathing in juvenile rats, and sensitizes the respiratory network to re‐exposure to ethanol, which does not seem to involve GABAergic neurotransmission.