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Lipoprotein disorders are a major risk factor for atherosclerotic neuro-cardiovascular disease (ACVD) and are heavily influenced by lifestyle, including alcohol drinking. Moderate drinkers have a lower ACVD risk than abstainers due to their higher levels of high-density lipoprotein (HDL) cholesterol, an important protective factor against ACVD. On the contrary, heavy drinking increases ACVD risk. According to an extensive literature body, ethanol intoxication modifies lipid serum profile and induces endothelial dysfunction. Single nucleotide polymorphisms may influence the relationship between alcohol drinking, HDL cholesterol level, and atherosclerotic risk. The risk of ACVD in heavy drinkers seems enhanced in patients with apolipoprotein E4 allele, interleukin- 6-174 polymorphism, and cholesteryl ester transfer protein TaqIB polymorphism. Apolipoprotein E4 is a known risk factor for ACVD, while apolipoprotein E2 has mixed effects. Therefore, even if a “protective role” may be attributed to moderate drinking, this effect cannot be extended to everyone.

The nerve growth factor (NGF) belongs to the family of neurotrophic factors. Initially discovered as a signaling molecule involved in the survival, protection, differentiation, and proliferation of sympathetic and peripheral sensory neurons, it also participates in the regulation of the immune system and endocrine system. NGF biological activity is due to the binding of two classes of receptors: the tropomyosin-related kinase A (TrkA) and the low-affinity NGF pan-neurotrophin receptor p75. Alcohol Use Disorders (AUD) are one of the most frequent mental disorders in developed countries, characterized by heavy drinking, despite the negative effects of alcohol on brain development and cognitive functions that cause individual’s work, medical, legal, educational, and social life problems. In addition, alcohol consumption during pregnancy disrupts the development of the fetal brain causing a wide range of neurobehavioral outcomes collectively known as fetal alcohol spectrum disorders (FASD). The rationale of this review is to describe crucial findings on the role of NGF in humans and animals, when exposed to prenatal, chronic alcohol consumption, and on binge drinking.

Patients with alcohol use disorder (AUD) do not manifest homogeneous clinical symptoms. Various studies described both cognitive impairments and psychiatric disorders among people with AUD. This disorder is one of the most frequent mental disorders in developed countries, due to excessive alcohol consumption. Alcohol is toxic as it increases the production of reactive oxygen species (ROS) and can cause dependence. This causes negative effects on brain development and cognitive functions that affect the individual's work, health, and social life. Current pharmacology treatment for alcohol addiction is based on direct action against the neurotransmitters involved in alcohol dependence. AUD patients without comorbid psychiatric disorders or severe cognitive deficits are defined as "pure alcoholics". To date, poor is known about effective treatments for this typology of AUD patients. Psychotherapy is largely used in resolving many psychiatric disorders, including substance use disorders. Motivational enhancement therapy (MET) and cognitive-behavioral therapy (CBT) are two psychotherapies used to achieve and maintain abstinence in patients affected by substance use disorders. This short review aims to describe two CBT and MET and to present the advantages and disadvantages of these two psychotherapies in the treatment of AUD.

Alcohol consumption during pregnancy and lactation is a widespread preventable cause of neurodevelopmental impairment in newborns. While the harmful effects of gestational alcohol use have been well documented, only recently the role of paternal preconceptual alcohol consumption (PPAC) prior to copulating has drawn specific epigenetic considerations. Solid human and animal model data demonstrated that PPAC may affect sperm function eliciting oxidative stress. In newborns, PPAC may induce changes in the behavior, cognitive functions and emotional responses. Furthermore, PPAC may elicit neurobiological disruptions, visuospatial impairments, hyperactivity disorders, motor skill disruptions, hearing loss, endocrine and immune alterations, reduced physical growth, placental disruptions and metabolic alterations. Neurobiological studies on PPAC disclosed also changes in brain function and structure by the disruption of the growth factors pathways. In particular, as shown in animal model studies PPAC alters brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) synthesis and release. This review shows that the crucial topic of lifelong disabilities induced by PPAC and/or gestational alcohol drinking is quite challenging at the individual, societal, and familial levels. Since a nontoxic drinking behavior before pregnancy (for both men and women) during pregnancy and lactation cannot be established the only suggestion for couples planning pregnancies is to completely avoid the consumption of alcoholic beverages.

Background: Fetal alcohol spectrum disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with fetal alcohol syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking also induces oxidative stress. Hypothesis/Objective: The present study aimed to investigate the potential association between neurotrophins, neuroinflammation, and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). Methods: Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as free oxygen radicals test (FORT) and free oxygen radicals defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-β, and TNF- α) involved in neuroinflammatory and oxidative processes have been investigated. Results: We demonstrated low serum levels of NGF and BDNF in pre-pubertal FASD children with respect to healthy controls. These changes were associated with higher serum presence of TNF- α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10, and IL-1α1 in the analyzed female compared to male children. Conclusion: The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

Background: Ethyl glucuronide (EtG) is a metabolite of ethanol used as a marker of alcohol drinking and is identified in urine. Gestational alcohol drinking harms the fetus, so disclosing any form of use and abuse of this substance during pregnancy is crucial. Many discovery methods have been planned to overcome this question, including using screening questionnaires as the AUDIT-C, T-ACE/TACER-3, and TWEAK. Aim: The aim and novelties of this study were to compare biochemical data from urinary EtG assays (cut-off 100 ng/mL for risking drinking behavior) with the outcome of questionnaires and of a food diary routinely used in our hospital; moreover, for the first time, we analyzed in pregnant women the EtG values normalized by the amount of creatinine excreted according to methods previously established. Methods: Random urine samples were collected from 309 pregnant women immediately after being interviewed. EtG was quantified using an enzyme immunoassay, and urinary creatinine was assessed using an enzymatic colorimetric method. Women who had not exhaustively answered one of the questionnaires or refused to provide urine samples were excluded. Finally, 309 women were considered for this study. Urine creatinine measurements were performed to determine if urine dilution might have resulted in false negatives in the challenge study. In order to accomplish this objective, as urinary creatinine concentrations are, on average, approximately 1 mg/mL, we used a normalized value of 100 ng EtG/mg Creatinine. Results: Our data show that 20.4% of the pregnant women in the study were over the established normalized cut-off value. Poor to null concordance (unweighted k < 0.2) was found between EtG data and the screening interviews showed, on average, lower levels of alcohol consumption. Conclusion: This study provides evidence that the assessment of maternal alcohol consumption during pregnancy, only indirectly estimated with questionnaires and food diary, can produce misleading results.

Background Vaginal digital examination is considered the gold standard to evaluate patients during labor and delivery. However, transperineal ultrasound has been suggested as an effective tool in determining fetal head station during labor. Angle of progression (AOP), head-perineal distance (HPD) and head-symphysis distance (HSD) are reliable parameters to assess fetal head station during labor. The study aims were to evaluate how midwives can use AOP, HSD, HPD to assess the accuracy of digital vaginal exploration limited to the fetal head station. Methods Trained midwives for ultrasound analyses performed transperineal ultrasounds during the first stage of labor with 2D-convex probe in 62 pregnant women at term with a single fetus in cephalic presentation. Immediately before the intrapartum ultrasound, the birth attendant performed a digital examination to assess cervical dilatation and head station. The ultrasound scans were compared to the digital vaginal examination through the Tutschek's formula. Results AOP was wider in women who delivered vaginally without any complication if compared to "complicated delivery" group. HPD and HSD were greater in women who underwent an operative vaginal delivery or caesarean section. The vaginal exploration accuracy was 34%, but when ±1 cm was considered as tolerated, the overall accuracy was 74.19%. Conclusions Midwives may include ultrasounds in their clinical practice after adequate training or under the supervision of an ultrasound professional as an adjunct tool during labor to evaluate its progress and prevent any deviation from physiology.

Gemma Battagliese was not included as an author in the original publication [...]

Breastfeeding success is determined by early skin to skin contact, early initiation of breastfeeding, rooming-in, baby-led breastfeeding, creation of a favorable environment, specific training of health professionals, and continuity of care.To investigate the women's satisfaction regarding the care and support received in the first days after childbirth.A questionnaire of 24 items was administered to mothers before discharge, from May to September 2019 at the University Hospital of Modena.The predictive variables of exclusive breastfeeding were the delivery mode, age at birth and parity. The multivariate analysis showed that a high satisfaction score was associated with vaginal birth (OR=2.63, p=0.005), rooming-in during the hospitalization (OR=8.64, p0.001), the skin to skin contact (OR=6.61, p=0.001) and the first latch-on within 1 hour after birth (OR=3.00, p=0.02).Mothers' satisfaction is one of the important factors of positive experience during hospital stay and of better health outcomes.

The aim of this study was to develop a questionnaire that allows researchers to investigate and measure the impact of physical disability on pregnancy and the management of motherhood. Such a questionnaire requires good internal consistency.The tool was developed following a study conducted in 2013 in the United States consisting of a semi-structured interview with open-ended questions. A team of three experts drafted and refined the questions, generating 31 retrospective, self-rated, and predefined questions (answered using a 5-point Likert scale). A statistical analysis of the instrument was also included, to assess its reliability and internal consistency.The Pregnancy and Motherhood Evaluation Questionnaire (PMEQ) was prepared. It is a self-administered questionnaire consisting of an initial section and three subscales. In this phase of the study, 35 women with different pathologies leading to physical disability were recruited and completed the questionnaire. The PMEQ was found to have a good internal consistency. Cronbach'sThe PMEQ has proven to be a valid, reliable, and rapid administrative tool useful for investigating and measuring the impact of physical disability on the management of pregnancy and motherhood.IMPLICATION FOR REHABILITATIONThis study provides researchers and clinicians a new tool for the evaluation of motherhood and pregnancy in women with physical disabilities.The PMEQ has proven to be a valid, reliable, and rapid administrative tool (10 min) useful for investigating and measuring the impact of physical disability on the management of pregnancy and motherhood.It is a new tool useful in both clinical and research practice to underline the importance of carrying out preventive and woman-centered assistance interventions.This tool is useful for promoting the autonomous management of pregnancy and motherhood in women with physical disabilities, and improving these women's quality of life and sense of satisfaction and competence in managing maternal tasks.

Polyphenols are antioxidants contained in plants as olive and grape. As part of the Mediterranean diet, they may decrease the risk of cancer, of chronic and neurodegenerative diseases. Alcohol consumption plays a detrimental effect on health, causing tissue damage and disrupting the metabolism of Neurotrophins (NTs). NTs are crucial proteins for the life cycle of neuronal and non-neuronal cells. Alcohol abuse elicits changes in NTs levels in the brain and in other target organs, however, it was observed minor damage in animals early exposed to red wine, probably due to the antioxidant effects of polyphenols. Indeed, data show that resveratrol or other polyphenols extracted from the olive can effectively counteract serum free radicals’ formation caused by chronic alcohol intake, contrasting also alcohol-induced NTs liver elevation. The aim of the present review is to update pieces of evidences about the antioxidant properties of polyphenols and their role in counteracting alcohol-induced damage.

Ethyl glucuronide (EtG) is an ethanol metabolite and EtG is used as a biomarker of alcohol drinking. EtG can be detected in the blood and in several biological matrices including urine, hair and nails. Alcohol consumption during pregnancy is a strong risk factor for fetus health so in the recent years different strategies to reveal alcohol use have been planning including the use of screening questionnaires as the AUDIT-C, T-ACE and TWEAK. The present study aims to investigate in pregnant women the specificity and predictive value of the AUDIT-C, T-ACE and TWEAK plus a food diary in use in Sapienza University Hospital compared with the results of urine EtG measurement. Seventy pregnant women were enrolled and examined. Urine samples were provided by pregnant women immediately after the interviews. EtG determinations were performed by Enzyme Immunoassay with a cut-off established at 100 ng/mL. Data show that 34.28% of the enrolled pregnant women overcame the EtG cut off. No direct correlation was found between EtG data and the alcohol screening interviews showing lower levels of alcohol consumption, although T-ACE revealed the same at risk percentage. However, a significant concordance was observed with food diary data and T-ACE only in patients with higher EtG urinary concentration. This study provides clinical evidence that the diagnosis of maternal alcohol consumption during pregnancy only based on indirect methods, such as questionnaires and food diary, may significantly underestimate alcohol use.

Women with disabilities feel the desire for motherhood as much as women without special clinical needs. Their fertility is often not impacted by disability and they can have children. However, several issues must be considered, depending on the physical, mental or developmental disability. Women with a physical disability often experience higher risks of caesarean section, preterm birth, growth restriction and low birth weight when compared to controls. Women with intellectual or developmental disabilities are often young, unmarried, unemployed and have limited access to care. They often struggle following instructions or recognizing the conditions that require medical help. They are more likely to experience preeclampsia, diabetes, venous thromboembolism, cesarean delivery, infant low birth weight, preterm birth, neonatal intensive care unit admission, and perinatal death. Moreover, an association between psychiatric morbidity and alcohol abuse was proved by several pieces of evidence and it can cause serious damage to fetus and newborn causing Fetal Alcohol Spectrum Disorders. Fetus and the newborn of disabled mothers are exposed to specific risks depending on the mother's conditions: the main risk fetuses are exposed to during pregnancy is exposure to drugs and therapies which cannot be suspended and whose effects over pregnancy are not known. Moreover, some conditions causing maternal disability could elevate the risk for the baby to be similarly affected. It is important that both women and men with disabilities could be provided with accurate, accessible, and understandable information about sexual health and options regarding contraception and reproduction. It's important for women with disabilities to have the chance to discuss sexual matters, pregnancy desires and concerns with healthcare providers so they can provide appropriate screenings, contraceptive services, preconception, and prenatal care. Among healthcare providers, midwives are the frontline healthcare professionals who have the role, the possibility and the education to perform influential counseling on women about lifestyles and reproductive health.

The nerve growth factor (NGF) belongs to a family of proteins named neurotrophins, consisting of NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5 and NT-6. NGF regulates a large number of physiological mechanisms that result in neurotrophic, metabotrophic and/or immunotrophic effects. Neurodegenerative diseases, including Alzheimer disease, psychiatric disorders (e.g. depression and schizophrenia) and brain parasitic infection have in common the effect of changing the brain levels of neurotrophins, in particular NGF. The contribution of both NGF and its receptor TrkA in such events and the recent promising results of NGF based therapies are here presented and discussed.

Down Syndrome (DS) is the most common chromosomal disorder. Although DS individuals are mostly perceived as characterized by some distinct physical features, cognitive disabilities, and cardiac defects, they also show important dysregulations of immune functions. While critical information is available for adults with DS, little literature is available on the neuroinflammation in prepubertal DS children. We aimed to evaluate in prepubertal DS children the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), oxidative stress as free oxygen radicals defense (FORD), free oxygen radicals test (FORT), and cytokines playing key roles in neuroinflammation and oxidative processes as TNF-α, TGF-β, MCP-1, IL-1α, IL-2, IL-6, IL-10, and IL-12. No differences were found in NGF between DS children and controls. However, BDNF was higher in DS subjects compared to controls. We also did not reveal changes in FORD and FORT. Quite interestingly, the serum of DS children disclosed a marked decrease in all analyzed cytokines with evident differences in serum cytokine presence between male and female DS children. In conclusion, the present study evidences in DS prepubertal children a disruption in the neurotrophins and immune system pathways.

Objectives Uncontrolled ingestion of alcohol has dramatic consequences on the entire organism that are also associated with the oxidation process induced by alcohol and elevate radical oxygen species. Resveratrol, a nonflavonoid phenol, shows well-documented antioxidant properties. We investigated the potential antioxidant ability of this natural compound in a mouse model of alcohol addiction. Methods We administered (per os) for 60 d 10 mg · kg–1 · d–1 of resveratrol in alcoholic adult male mice. Oxidative stress was evaluated by measuring serum–free oxygen radicals defense and free oxygen radical levels. Resveratrol metabolites were measured in the serum of mice that were administered with resveratrol. Finally, the effect of resveratrol on the alcohol-induced alteration of brain-derived neurotrophic factors (BDNF) in the liver was investigated. Results Prolonged consumption of resveratrol strongly counteracts serum radical oxygen species formation caused by chronic alcohol intake without effects on natural, free oxygen radical defense. The presence of resveratrol metabolites in the serum only of animals supplemented with resveratrol potentiates the evidence that the antioxidant effect observed is due to the ingestion of the natural compound. Moreover, resveratrol supplementation can counteract alcohol-induced BDNF elevation in the liver, which is the main target of organ alcohol-induced damage. Conclusions The consumption of resveratrol through metabolite formation may play a protective role by decreasing free radical formation and modulating the BDNF involved in hepatic disruption induced by chronic alcohol consumption. Further investigation into the mechanism underlying the protective effect could reinforce the potential use of resveratrol as a dietary supplement to prevent damage associated with chronic alcohol abuse.

In this study, we investigated in people suffering from alcohol use disorder (AUD) with or without dual diagnosis (concomitant psychiatric disability) how they feel their dependence condition. We predicted that AUD people with a dual diagnosis could feel potentiated their addiction.Alcohol habits and psychiatric conditions of 183 AUD men and 62 AUD women were measured by using the DSM-5, the severity of alcohol dependence questionnaire (SADQ), the alcohol anamnesis and psychiatric examination by the symptom check list 90-R (SCL-90-R).We have shown that alcohol drinking does not correlate with both psychiatric examination and self-reported psychopathology. SADQ shows that severe alcohol dependence correlates with highest psychiatric symptoms and with the levels of alcohol consumption.This finding suggests that high SADQ scores may represent a tool to early disclose only patients with dual diagnosis. SADQ may provide information to address pharmacological interventions because revealing aspects of the dark side of addiction potentiated by AUD associated psychopathology.

Neurotrophins (NTs) are a family of polypeptides whose functions have been extensively studied in the past two decades. In particular, Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) play a major role in the development, nutrition and growth of the central and peripheral nervous system and in the pathogenesis of neurodegenerative, cardiometabolic and (auto)immune diseases. However, NGF and BDNF have subtle functions for follicular development, implantation, and placentation. This short narrative review summarizes the existing evidence, published between 2000 and 2019, about the role of NTs in many different conditions that might affect women during and after pregnancy such as preeclampsia, gestational diabetes, obesity, depression, anxiety, smoking and alcohol abuse. Literature suggests that the dysregulation of synthesis and release of NTs may lead to decisive effects on both maternal and fetal health. Some piece of evidences was found about a possible association between NGF/BDNF and breastfeeding. Additional studies on human models are necessary to further characterize the role of NTs in life-changing experiences like labor and delivery.

Fetal alcohol spectrum disorders (FASDs) are a group of negative conditions occurring in children exposed to alcohol during gestation. The early discovery of FASD is crucial for mother and infant follow-ups. In this study, we investigated in pregnant women the association between urine ethylglucuronide (EtG-a biomarker of alcohol drinking) and indicators of the physical characteristics of FASD by prenatal ultrasound in the second trimester of gestation. We also correlated these data with the AUDIT-C, T-ACE/TACER-3, TWEAK, and food habit diary, screening questionnaires used to disclose alcohol drinking during pregnancy. Forty-four pregnant women were randomly enrolled and examined for ultrasound investigation during the second trimester of gestation. Urine samples were provided by pregnant women immediately after the routine interviews. EtG determinations were performed with a cutoff established at 100 ng/mL, a value indicating occasional alcohol drinking. Fifteen of the enrolled pregnant women overcame the EtG cutoff (34.09%). Analysis of variance (ANOVA) revealed that the fetuses of the positive EtG pregnant women had significantly longer interorbital distance and also significantly increased frontothalamic distance (P's < 0.02). Quite interestingly, no direct correlation was found between EtG data and both food diary and AUDIT-C. However, a significant correlation was observed between urinary EtG and T-ACE (r = 0.375; P = 0.012) and between urinary EtG and TWEAK (r = 0.512; P < 0.001) and a concordance with all questionnaire for EtG values higher than 500 ng/mL. This study provides clinical evidence that the diagnosis of maternal alcohol consumption during pregnancy by urine EtG may disclose FASD-related damage in the fetus.

The nerve growth factor (NGF) belongs to a family of proteins termed neurotrophins, consisting of NGF, brain-derived neuro- trophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5 and NT-6. Today, NGF is well recognized to mediate a large number of trophobiological actions resulting in neurotrophic, immunotrophic and/or metabotrophic effects. The pathobiology of neurode- generative diseases, including Alzheimer disease, psychiatric disorders (e.g. depression and schizophrenia) and brain parasitic infections have in common the effect of altering the brain levels of neurotrophins and in particular NGF. The involvement of NGF and its TrkA receptor in these pathologies and the recent promising results of NGF therapies are presented and discussed.

Emerging researches from human and animal models have shown the role of ethanol in innate immune system modulation, particularly in the central nervous system. The activation of receptors of the innate immunity, Toll-like receptors and nucleotide- binding oligomerization domain-like (NOD-like) receptors, triggers the signaling pathways that bring to the production of pro-inflammatory cytokines and chemokines, which, in turn, provokes neuroinflammation and neural damage. The neuroimmune system response to ethanol intake, in specific brain regions such as amygdala, hippocampus and frontal cortex, is involved in addiction and in behavioural deficits observed in alcoholism. In murine models, the knockout for Toll-like or NODlike receptors abolishes most of the effects of ethanol on the immune system and preserves these mice from neural damage, neuroinflammation and alcohol dependence. Molecular targeting of immune system pathways is a new and promising area of research for the discovery of new biomarkers for neuroinflammation and for the development of novel pharmacotherapies in order to treat neurological and behavioural consequences of ethanol addiction. Biomed Rev 2017; 28: 49-61. Keywords: ethanol addiction, neuroinflammation, neuroimmunity, Toll-like receptors, NOD-like receptors, inflammasomes

The present study was aimed at examining spatial learning and memory, in 33 men and 12 women with alcohol use disorder (AUD) undergoing ethanol detoxification, by using a virtual Morris task. As controls, we recruited 29 men and 10 women among episodic drinkers without a history of alcohol addiction or alcohol-related diseases. Elevated latency to the first movement in all trials was observed only in AUD persons; furthermore, control women had longer latencies compared with control men. Increased time spent to reach the hidden platform in the learning phase was found for women of both groups compared with men, in particular during trial 3. As predicted, AUD persons (more evident in men) spent less time in the target quadrant during the probe trial; however, AUD women had longer latencies to reach the platform in the visible condition during trials 6 and 7 that resulted in a greater distance moved. As for the probe trial, men of both groups showed increased virtual locomotion compared with the women of both groups. The present investigation confirms and extends previous studies showing (i) different gender responses in spatial learning tasks, (ii) some alterations due to alcohol addiction in virtual spatial learning, and (iii) differences between AUD men and AUD women in spatial-behaviour-related paradigms.

Fetal Alcohol Spectrum Disorders (FASD) is a term used to describe the broad spectrum of pathologies and disorders caused by alcohol exposure in uterus. Since alcohol is able to directly cross the placental barrier, alcohol intake during pregnancy causes a broad range of symptoms whose severity can greatly vary in degree. It is already well established that Ethanol exhibits teratogenic effects resulting in growth delays, physical and specific facial anomalies, neurological defects including intellectual disabilities and behavioral problems. Since it is not possible yet to establish a safe threshold of consumption, the only feasible recommendation is the total abstention from alcohol during pregnancy. This work firstly presents an overview on FASD and reviews specific methodologies to overcome difficulties related to the investigation of alcohol behavior in pregnant women. Subsequently, different protocols of intervention are proposed according to different styles of alcohol consumption. The final goal is to provide clinicians with a range of methods in order to prevent damage in the newborns.

Here, an overview of neurophysiological, pharmacological and genetic research on the role of neuropeptide tyrosine (NPY) in ethanol consumption and withdrawal is presented. NPY is abundantly expressed in the extended amygdala and is critically involved in the regulation of negative affective states in rats, also is involved with neurobiological responses to ethanol and other drug of abuse. Genetic, molecular and pharmacological evidences suggest that NPY is an important neurobiological substrate for the predisposition to alcoholism. Administration, as well as the withdrawal of ethanol, alters central NPY expression. Alcohol-preferring rats exhibit basal NPY deficits in central amygdala. In the latter, NPY may rescue dependence-induced increases in anxiety and alcohol drinking. Low NPY levels in some brain regions following ethanol withdrawal contribute to the increased sensitivity to seizure and the heightened levels of anxiety characteristic of withdrawal responses. Mice with deletion of NPY gene exhibit a high-anxiety, high-alcohol-drinking phenotype. Pharmacological and genetic manipulations suggest that central NPY signaling modulates ethanol consumption via Y1, Y2, and Y5 receptors. Analysis of chromosomal regions (QTLs) associated with alcohol consumption identified NPY as one of the genes that influence alcohol dependence and as a promising target for pharmacotherapeutics to combat alcohol associated disorders. Consequently, NPY is a potentially new pharmacological target for the treatment of alcohol diseases.