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In the rat, prenatal exposure to diazepam (DZ) induces a permanent reduction in GABA/BZ receptor (R) function and behavioural abnormalities. Environmental modifications during early stages of life can influence brain development and induce neurobiological and behavioural changes throughout adulthood. Indeed, a subtle, periodic, postnatal manipulation increases GABA/BZ R activity and produces facilitatory effects on neuroendocrine and behavioural responses. We here investigated the impact of prenatal treatment with DZ on learning performance in adult 3- and 8-month-old male rats and the influence of a brief, periodic maternal separation on the effects exerted by prenatal DZ exposure. Learning performance was examined employing a non-aversive spatial, visual and/or tactile task, the "Can test". Behavioural reactivity, emotional state and fear/anxiety-driven behaviour were also examined using open field (OF), acoustic startle reflex (ASR) and elevated plus-maze (EPM) tests. A single daily injection of DZ (1.5 mg/kg, s.c.), over gestational days (GD) 14-20, induced, in an age-independent manner, a severe deficit in learning performance, a decrease in locomotor and explorative activity and an increase in peak amplitude in the ASR. Furthermore, anxiety-driven behaviour in EPM was disrupted. Daily maternal separation for 15 min over postnatal days 2-21 exerted opposite effects in all the paradigms examined. Prenatally DZ-exposed maternal separated rats, in contrast to respective non-separated rats, showed an improvement in learning performance, a decrease in emotionality and a normalization of the exploratory behaviour in EPM. These results suggest that a greater maternal care, induced by separation, can serve as a source for the developing brain to enhance neuronal plasticity and to prevent the behavioural abnormalities induced by prenatal DZ exposure. © 2005 Elsevier B.V. All rights reserved.

The sleep-wake cycle plays a fundamental role in maintaining the physiological balance of our body. Its alteration favours the genesis of several organic alterations and diseases including sleep disorders and the consumption of several substances of abuse. It has been reported that the work activity, especially that carried out during the night, is able to influence the sleep-wake cycle, promoting the development of insomnia, which, in turn, would subject the worker to a stressful condition such as to encourage adverse behaviour such as the use/abuse of psychotropic substances. Based on the above premises, the aim of our research was to evaluate, in night workers: (i) the pattern of consumption of alcoholic beverages; (ii) the presence of insomnia; and (iii) the possible correlation between alcohol consumption and insomnia disorder. We used the AUDIT-C test (the abbreviated version of the Alcohol Use Disorders Identification Test) and the Insomnia Severity Index to assess alcohol consumption and insomnia disorder, respectively. All questionnaires were completed by workers of both sexes belonging to different types of work activities, exclusively day or night. The results of our research show a higher propensity of night workers to consume alcoholic beverages than those who work during daytime hours, often in binge-drinking mode. In addition, an increase in the amount of alcohol consumed was found to be related to insomnia disorder, especially in night workers. This study provides further awareness of the importance of the negative impact of alcohol consumption on sleep quality in night workers.

Vertigo is not itself a disease, but rather a symptom of various syndromes and disorders that jeopardize balance function, which is essential for daily activities. It is an abnormal sensation of motion that usually occurs in the absence of motion, or when a motion is sensed inaccurately. Due to the complexity of the etiopathogenesis of vertigo, many pharmacological treatments have been tested for efficacy on vertigo. Among these drugs, cinnarizine, usually given together with dimenhydrinate, appears to be the first-line pharmacotherapy for the management of vertigo and inner ear disorders. Based on these considerations, the present non-interventional study aimed to investigate the clinical efficacy and tolerability of a fixed combination of cinnarizine (20 mg) and dimenhydrinate (40 mg) in patients suffering from vertigo-related symptoms. To this end, we enrolled 120 adults—70 males, and 50 females—with an average age of 64 years. Before beginning pharmacological treatment, all patients were screened for the intensity of vertigo, dizziness, and concomitant symptoms through the Visual Scale of Dizziness Disorders and Dizziness Handicap Inventory scales. At the end of the anamnestic evaluation, patients received the fixed-dose combination of cinnarizine (20 mg) plus dimenhydrinate (40 mg) 3 times daily, for 60 days. The results of this study provide further insight regarding the efficacy of the fixed combination when used to reduce symptoms of vestibular vertigo of central and/or peripheral origin, after both the 15- and 60-day therapies. Independent of the type of vertigo, the fixed combination was able to reduce dizziness- and vertigo-associated symptoms in more than 75% of all patients treated, starting from 15 days of therapy, and improving 60 days after starting the therapy. Interestingly, we also found differences between male and female patients in the framework of the pharmacological effects of therapy. This study provides further details concerning the therapeutic efficacy of the fixed combination of cinnarizine and dimenhydrinate, and also focuses attention on the possibility that these drugs could act in a gender-specific manner, paving the way for further research.

While a lot is known about the mechanisms promoting aversive learning, the impact of rewarding factors on memory has received comparatively less attention. This research investigates reward-related explicit memory in male rats, by taking advantage of the emotional-object recognition test. This is based on the prior association, during conditioned learning, between a rewarding experience (the encounter with a receptive female rat) and an object; afterwards rat discrimination and recognition of the â emotional objectâ is recorded in the presence of a novel object, as a measure of positive limbic memory formation. Since endocannabinoids are critical for processing reward and motivation, the consequences of the stimulation of cannabinoid signalling are also assessed by the administration of WIN 55,212-2 at pre- and post-conditioning time. Our results show that rats encode the association between object and rewarding experience, form positive limbic memory of the emotional object, and retrieve this information in the face of novelty. Stimulation of the cannabinoid system at pre-conditioning time is able to strengthen reward-related explicit memory in the presence of novelty, whereas post-conditioning activation increases approach behaviour to novel stimuli. The assessment of limbic memory by the emotional-object recognition test can help unveiling the addictive and confounding properties of psychotropic drugs.

Work-related stress can induce a break in homeostasis by placing demands on the body that are met by the activation of two different systems, the hypothalamic&ndash, pituitary&ndash, adrenal axis and the sympathetic nervous system. Night-shift work alters the body&rsquo, s exposure to the natural light&ndash, dark schedule and disrupts circadian (daily) rhythms. The greatest effect of night-shift work is the disruption of circadian rhythms. The impact that these disruptions may have on the pathogenesis of many diseases, including cancer, is unknown. This study aims to discover the relationship among three different job activities of security guards and their stress-related responses by evaluating salivary cortisol levels and blood pressure. Methods: Ninety security guards, including night-time workers and night-time and daily-shift workers, were recruited for this study. Each security guard provided two saliva samples before and after three scheduled time points: (i) at 22:00, (ii) at 06:30, and (iii) at 14:00. Results: The results of the study showed a significant alteration in cortisol levels. Night-time shift cortisol levels significantly increased before and after the work shifts. A physiological prevalence of the vagal tone on the cardiocirculatory activity was found during night-shift work. Conclusions: This study indicates that cortisol levels and blood pressure are sensitive markers of biological responses to severe work stress. Shift-change consequences may occur at the end of the night shift when there is a significant increase in the cortisol level and a significant variation in cardiovascular parameters.

The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence. In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction.

Rationale: In depressive disorders, one of the mechanisms proposed for antidepressant drugs is the enhancement of synaptic plasticity in the hippocampus and cerebral cortex. Previously, we showed that the muscarinic acetylcholine receptor (mAChR) agonist oxotremorine (Oxo) increases neuronal plasticity in hippocampal neurons via FGFR1 transactivation. Objectives: Here, we aimed to explore (a) whether Oxo exerts anxiolytic effect in the rat model of anxiety-depression-like behavior induced by chronic restraint stress (CRS), and (b) if the anxiolytic effect of Oxo is associated with the modulation of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF2), and phosphorylated Erk1/2 (p-Erk1/2) levels in the dorsal or ventral hippocampus and in the medial prefrontal cortex. Methods: The rats were randomly divided into four groups: control unstressed, CRS group, CRS group treated with 0.2mg/kg Oxo, and unstressed group treated with Oxo. After 21days of CRS, the groups were treated for 10days with Oxo or saline. The anxiolytic role of Oxo was tested by using the following: forced swimming test, novelty suppressed feeding test, elevated plus maze test, and light/dark box test. The hippocampi and prefrontal cortex were used to evaluate BDNF and FGF2 protein levels and p-Erk1/2 levels. Results: Oxo treatment significantly attenuated anxiety induced by CRS. Moreover, Oxo treatment counteracted the CRS-induced reduction of BDNF and FGF2 levels in the ventral hippocampus and medial prefrontal cerebral cortex Conclusions: The present study showed that Oxo treatment ameliorates the stress-induced anxiety-like behavior and rescues FGF2 and BDNF levels in two brain regions involved in CRS-induced anxiety, ventral hippocampal formation, and medial prefrontal cortex.

Background Emotionally salient experiences induce the formation of explicit memory traces, besides eliciting automatic or implicit emotional memory in rodents. This study aims at investigating the implementation of a novel task for studying the formation of limbic memory engrams as a result of the acquisition- and retrieval- of fear-conditioning – biased declarative memory traces, measured by animal discrimination of an “emotional-object”. Moreover, by using this new method we investigated the potential interactions between stimulation of cannabinoid transmission and integration of emotional information and cognitive functioning. New method The Emotional-Object Recognition task is composed of 3 following sessions: habituation; cued fear-conditioned learning; emotional recognition. Rats are exposed to Context “B chamber” for habituation and cued fear-conditioning, and tested in Context “A chamber” for emotional-object recognition. Results Cued fear-conditioning induces a reduction in emotional-object exploration time during the Emotional-Object Recognition task in controls. The activation of cannabinoid signalling impairs limbic memory formation, with respect to vehicle. Comparison to existing methods The Emotional-Object Recognition test overcomes several limitations of commonly employed methods that explore declarative-, spatial memory and fear-conditioning in a non-integrated manner. It allows the assessment of unbiased cognitive indicators of emotional learning and memory. Conclusions The Emotional-Object Recognition task is a valuable tool for investigating whether, and at what extent, specific drugs or pathological conditions that interfere with the individual affective/emotional homeostasis, can modulate the formation of emotionally salient explicit memory traces, thus jeopardizing control and regulation of animal behavioural strategy.

The aims of this study were to determine the distribution of risk factors associated with tinnitus analysing their role in the development of tinnitus and the effects of their interaction; to evidence the importance of a suitable and adequate clinical and audiologic assessment to avoid those modifiable risk factors responsible for cochlear dysfunction and tinnitus onset. 46 subjects with tinnitus and 74 controls were studied according to: age, sex, Body Mass Index (BMI), neck circumference, tobacco smoking, feeling fatigue or headache, self reporting snoring, hypertension, diabetes, coronary heart disease, and/or hyperlipidemia, and laboratory finding as lipid profile and levels of reactive oxygen metabolites (d-ROM). Audiological assessment was performed by multi-frequency audiometry (PTA0.5–16 kHz) and transient-evoked otoacoustic emissions (TEOAE diagnostic). Univariate analysis was performed to examine the association between determinants and occurrence of tinnitus; Mantel–Haenszel test (G.or) was used to investigate the joint effect of determinants on tinnitus. Tinnitus was more frequent among males with age >50 years; BMI >30 kg/m2, neck circumference >40 cm, headache, hypertension, hypercholesterolemia resulted significant risk factors for tinnitus (P < 0.0001). Tinnitus group had more comorbidity (P < 0.0001) and worse audiometric thresholds (60.87 Vs 21.62 % hearing loss; P < 0.0001) with respect to control group. The interaction between hypertension–BMI ≥ 30 kg/m2 (G.or = 8.45) and smoking–hypercholesterolemia (G.or = 5.08) increases the risk of tinnitus (P < 0.0001). Our results underline that several factors either individually or jointly contribute to tinnitus onset; a comprehensive knowledge about tinnitus risk factors and associated clinical conditions could contribute to minimizing this disorder.

Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study, we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/Kg, s. c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of spatial information-acquisition during the baseline training, and of memory retention in the longitudinal study. Furthermore, on the basis of PREGS pharmacological profile, the modulation of depressive-like behaviour was also evaluated in the forced swim test (FST). Our results indicate that acute PREGS induces: an improvement in spatial orientation-acquisition and in reference memory, during the baseline training; a strengthening effect on reference and working memory during the longitudinal study. A decrease in immobility time in the FST has also been recorded. In conclusion, PREGS exerts enhancing properties on acquisition, consolidation and retrieval of spatial information, probably due of improved hippocampal-dependent memory processes. The additional antidepressant effect observed in the FST can provide further evidence in support of the potential of PREGS as a therapeutic tool for the treatment of cognitive deficits associated with mood disorders. This article is part of a Special Issue entitled: insert SI title.

Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/kg, s.c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of both spatial orientation–acquisition and object discrimination in a simple and in a complex version of the visual task. Electrophysiological recordings were also performed in vivo , after acute PREGS systemic administration in order to investigate on the neuronal activation in the hippocampus and the perirhinal cortex. Our results indicate that, PREGS induces an improvement in spatial orientation–acquisition and in object discrimination in the simple and in the complex visual task; the behavioural responses were also confirmed by electrophysiological recordings showing a potentiation in the neuronal activity of the hippocampus and the perirhinal cortex. In conclusion, this study demonstrates that PREGS systemic administration in rats exerts cognitive enhancing properties which involve both the acquisition and utilization of spatial information, and object discrimination memory, and also correlates the behavioural potentiation observed to an increase in the neuronal firing of discrete cerebral areas critical for spatial learning and object recognition. This provides further evidence in support of the role of PREGS in exerting a protective and enhancing role on human memory.

Alcohol abuse is a substantial and growing health problem in Western societies. In the last years in vivo and in vitro studies have suggested that males and females display a different alcohol drinking behaviour, with swingeing differences not only in the propensity for alcohol use but also in the metabolic and behavioural consequences. In this study we investigated, in adult female rats, ethanol self-administration and preference pattern using a 3-bottle paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on explorative behaviour in the open field (OF), and on spatial learning and reference memory in the Morris water maze (MWM) were also evaluated. Our results indicate that: (i) female rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; (ii) at the fourth week of the free-access paradigm rats show a lower explorative behaviour in the open field and a worsening in spatial memory retention in the Morris water maze. In conclusion our data suggest that, despite the ability to self-regulate alcohol intake, female rats suffer from relevant impairments in spatial memory retention and cognitive flexibility, displaying a sexually dimorphic modification in the adaptive strategies.

Background: Acetaldehyde (ACD), ethanol's first metabolite, has been reported to interact with the dopaminergic reward system, and with the neural circuits involved in stress response. Rats self-administer ACD directly into cerebral ventricles, and multiple intracerebroventricular infusions of ACD produce conditioned place preference. Self-administration has been largely employed to assess the reinforcing and addictive properties of most drugs of abuse. In particular, operant conditioning is a valid model to investigate drug-seeking and drug-taking behavior in rats. Methods: This study was aimed at the evaluation of (i) the motivational properties of oral ACD in the induction and maintenance of an operant-drinking behavior; (ii) ACD effect in a conflict situation employing the punishment-based Geller–Seifter procedure; and (iii) the onset of a relapse drinking behavior, following ACD deprivation. The lever-pressing procedure in a sound-attenuated operant-conditioning chamber was scheduled into 3 different periods: (i) training—rewarded responses with a fixed ratio 1; (ii) conflict—rewarded responses periodically associated with a 0.2 mA foot-shock; and (iii) relapse—rewarded lever presses following 1-week ACD abstinence. Results: Our results show that oral self-administrated ACD induced: a higher rate of punished responses in Geller–Seifter procedures; and the establishment of a relapse behavior following ACD deprivation. Conclusions: In conclusion, our results indicate that ACD is able to induce an operant-drinking behavior, which is also maintained besides the conflict procedure and enhanced by the deprivation effect, supporting the hypothesis that ACD itself possesses motivational properties, such as alcohol and other substances of abuse.

Chronic ethanol consumption is able to modify emotional behaviour and cognition in humans. In particular, the effects exerted by alcohol may depend on doses, time and modalities of administration. In this study we investigated, in adult male rats, ethanol self-administration and preference patterns using a 3-bottle choice paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on novelty-induced explorative behaviour in the open field, and on spatial learning and reference memory in the Morris water maze was also evaluated. Our results indicate that: (i) rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; (ii) at the fourth week of the free-access paradigm rats show a high explorative behaviour in the central squares of the open field and an improvement in spatial information processing in the new-place learning task of the Morris water maze. In conclusion our data suggest that, interestingly, rats exposed to the free-access paradigm were able to self-regulate their alcoholic intake, and indicated that a moderate alcohol consumption was able to induce an increase in behavioural reactivity and an enhancement in spatial learning flexibility.

BACKGROUND AND METHODS Ethanol (EtOH) activates hypothalamic-pituitary-adrenal (HPA) axis, resulting in adrenocorticotropin hormone, glucocorticoid release, and in modifications of the response of the axis to other stressors. The initial site of EtOH action within the HPA system seems to be the hypothalamus. Thus, to determine the mechanisms responsible for these effects, we investigated: (i) whether EtOH was able to release corticotrophic releasing hormone (CRH) from incubated hypothalamic explants; (ii) whether acetaldehyde (ACD), its first metabolite formed in the brain by catalase activity, might play a role in EtOH activity. To this aim, rat hypothalamic explants were incubated with: (i) medium containing EtOH at 32.6 x 10(3) microM; (ii) different concentration of ACD (1, 3, 10, and 30 microM); (iii) EtOH plus 3amino-1,2,4-triazole (3AT, 32 x 10(3) microM) an inhibitor of cerebral catalase; (iv) ACD plus D-penicillamine (DP, 50.3 x 10(3) microM) an ACD-trapping agent. CRH levels were evaluated by a radioimmunoassay. RESULTS Incubation with EtOH induced a 7-fold increase in CRH secretion, with respect to basal levels; ACD was able to stimulate CRH release in a dose-dependent manner; the inhibition of cerebral catalase by 3AT blocked EtOH-induced CRH outflow; the inactivation of ACD by DP reverted the ACD-stimulating effect on CRH secretion. CONCLUSIONS These data show that both EtOH and acetaldehyde are able to increase hypothalamic CRH release from the rat hypothalamus and that acetaldehyde itself appears to be the mediator of EtOH activity.

Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these experimental models, and by the co-administration of the selective and silent 5-HT1A antagonist WAY 100635. Results indicate that a single daily injection of 5MT to, pregnant dams from gestational days 12 to 21 (1 mg/kg s.c.), and to the pups from postnatal days 2 to 18 (0.5 mg kg s.c.), induce in the adolescent rat offspring: an increase in the percentage of entries and time spent on the open arms in the elevated plus maze; a reduction in locomotor activity and rearing frequency, and an increase in the time spent on the central areas in the open field test; a decrease in immobility and an increase in swimming in the forced swim test. Acute administration of LY 228729 (1.5 mg/kg s.c.) strongly decreases rearing frequency and increases peripheral activity in the open field test, and decreases immobility and increases swimming in the forced swim test both in perinatally vehicle and 5MT-exposed offspring. Co-administration of WAY 100635 (0.25 mg/kg s.c.) abolishes the effects exerted by LY 228729. These results suggest that, in the adolescent rat, perinatal exposure to 5MT enhances the stress-related adaptive behavioural responses, presumably through a predominant action on presynaptic 5-HT1A receptors and does not deteriorate the functional response of 5-HT1A receptors to selective agonist and antagonist compounds.

A reduction in 5-HT1A receptor response enhances learning and memory performance in rats. Pre- and postnatal treatment with 5-methoxytryptamine (5MT), a non-selective serotonergic agonist, and early handling, reduce the number of 5-HT1A receptors in neonatal and pre-pubertal rat progeny. The aim of this study was to investigate in adolescent male rats the consequences of pre- and postnatal treatment with 5MT and its interaction with early handling on an object-place association learning task, the "Can test", a motivated, non-aversive, spatial/object discrimination task. Results show that a single daily injection of 5MT from gestational days 12 to 21 (1 mg/kg s.c.) and from postnatal days 2 to 18 to pups (0.5 mg/kg s.c.), increases the level of activity and the number of correct responses, and decreases the number of reference memory errors in the progeny as adolescent, compared to vehicle-treated rats. Similar effects are observed following a daily, brief, maternal separation of the pups from postnatal days 2 until 21. Furthermore, when 5MT-treated rats underwent to early handling procedure, the effects induced by 5MT increased handling-induced facilitation of the object-place association. These results suggest that pre- and postnatal treatment with 5MT enhances learning in the "Can test", probably due to a reduction in 5-HT1A receptors in the hippocampus. Whether the potentiation exerted by pre- and postnatal 5MT on early handling effects may be related to a further damping of 5-HT1A receptor response is not yet assessed; however, our data demonstrate that this association is able to induce long-term facilitative effects on spatial learning performance in a non-aversive spatial/object discrimination task in the adolescent rat offspring.

Perinatal manipulations can lead to neurobehavioural changes in the progeny. In this study we investigated, in adolescent male rat offspring, the consequences of a single, intense prenatal stress induced by a 120 min-maternal immobilization at gestational day 16, and of a daily, brief maternal separation from postnatal day 2 until 21, on: unconditioned fear/anxiety-like behaviour in open field and in elevated plus-maze; learning performance in the "Can test", a non-aversive spatial and tactile/visual task; corticosterone plasma levels under basal and stress-induced conditions. Our results indicate that both prenatal stress and maternal separation procedures decrease emotionality and enhance learning performance. Maternal separation potentiates prenatal stress-induced effects in enhancing learning performance. Both basal and stress-induced corticosterone plasma levels are reduced following prenatal stress, maternal separation and the combination of two procedures. These findings suggest that a single, intense prenatal stress can enhance the adaptive stress-related responses in the progeny, probably due to the involvement of maternal factors. The synergistic effect of prenatal stress and maternal separation on learning performance may be due to a further damping of hypothalamic-pituitary-adrenal axis response in the progeny that better cope with the task administered.

Acetaldehyde, the first metabolite of ethanol, is active in the central nervous system, where it exerts motivational properties. Acetaldehyde is able to induce drinking behaviour in operant-conflict paradigms that resemble the core features of the addictive phenotype: drug-intake acquisition and maintenance, drug-seeking, relapse and drug use despite negative consequences. Since acetaldehyde directly stimulates dopamine neuronal firing in the mesolimbic system, the aim of this study was the investigation of dopamine D2-receptors' role in the onset of the operant drinking behaviour for acetaldehyde in different functional stages, by the administration of two different D2-receptor agonists, quinpirole and ropinirole. Our results show that acetaldehyde was able to induce and maintain a drug-taking behaviour, displaying an escalation during training, and a reinstatement behaviour after 1-week forced abstinence. Acetaldehyde operant drinking behaviour involved D2-receptor signalling: in particular, quinpirole administration at 0.03 mg/kg, induced a significant decrease in the number of lever presses both in extinction and in relapse. Ropinirole, administered at 0.03 mg/kg during extinction, did not produce any modification but, when administered during abstinence, induced a strong decrease in acetaldehyde intake in the following relapse session. Taken together, our data suggest that acetaldehyde exerts its own motivational properties, involving the dopaminergic transmission: indeed, activation of pre-synaptic D2-receptors by quinpirole, during extinction and relapse, negatively affects operant behaviour for acetaldehyde, likely decreasing acetaldehyde-induced dopamine release. The activation of post-synaptic D2-receptors by ropinirole, during abstinence, decreases the motivation to the consecutive reinstatement of acetaldehyde drinking behaviour, likely counteracting the reduction in the dopaminergic tone typical of withdrawal. These data further strengthen the evidence that acetaldehyde may play a crucial role as mediator of ethanol's central effects.

INTRODUCTION: Upper respiratory tract infection is a nonspecific term used to describe an acute infection involving the nose, paranasal sinuses, pharynx and larynx. Upper respiratory tract infections in children are often associated with Eustachian tube dysfunction and complicated by otitis media, an inflammatory process within the middle ear. Environmental, epidemiologic and familial risk factors for otitis media (such as sex, socioeconomic and educational factors, smoke exposure, allergy or duration of breastfeeding) have been previously reported, but actually no data about their diffusion among Sicilian children with upper respiratory tract infections are available. OBJECTIVE: To investigate the main risk factors for otitis media and their prevalence in Sicilian children with and without upper respiratory tract infections. METHODS: A case-control study of 204 children with upper respiratory tract infections who developed otitis media during a 3 weeks monitoring period and 204 age and sex-matched healthy controls. Seventeen epidemiologically relevant features were inventoried by means of standardized questionnaires and skin tests were performed. Univariate analysis and multivariate logistic regression analysis were used to examine the association between risk factors and occurrence of otitis media. RESULTS: Otitis media resulted strongly associated to large families, low parental educational attainment, schooling within the third years of life (p < 0.05); children were more susceptible to develop otitis media in the presence of asthma, cough, laryngopharyngeal reflux disease, snoring and apnea (p < 0.05). Allergy and urban localization increased the risk of otitis media in children exposed to smoke respectively of 166% and 277% (p < 0.05); the joint effect of asthma and presence of pets in allergic population increased the risk of recurrence of 11%, while allergy, cough and runny nose together increased this risk of 74%. CONCLUSIONS: Upper respiratory tract infections and otitis media are common childhood diseases strongly associated with low parental educational attainment (p = 0.0001), exposure to smoke (p = 0.0001), indoor exposure to mold (p = 0.0001), laryngopharyngeal reflux disease (p = 0.0002) and the lack of breast-feeding (p = 0.0014); an increased risk of otitis media recurrences was observed in the presence of allergy, persistent cough and runny nose (p = 0.0001). The modification of the identified risk factors for otitis media should be recommended to realize a correct primary care intervention. RESUMO INTRODUÇÃO: A infecção de vias aéreas superiores é uma denominação inespecífica, empregada na descrição de uma infecção aguda envolvendo o nariz, os seios paranasais, a faringe e a laringe. As infecções de vias aéreas superiores em crianças estão frequentemente associadas à disfunção da trompa de Eustáquio, complicando-se com otite média, um processo inflamatório da orelha média. Já foram relatados vários fatores de risco relacionados à otite média, incluindo os ambientais, epidemiológicos e familiares (p. ex., gênero, fatores socioeconômicos e educacionais, exposição ao tabaco, alergia ou duração do aleitamento materno), entretanto, não dispomos de dados sobre sua ocorrência entre crianças sicilianas com infecções de vias aéreas superiores. OBJETIVO: Investigar os principais fatores de risco para otite média e sua prevalência em crianças sicilianas com e sem infecções de vias aéreas superiores. MÉTODO: Um estudo de caso-controle de 204 crianças com infecções de vias aéreas superiores apresentando otite média durante um período de monitoração de três semanas e 204 controles saudáveis compatíveis em idade e gênero. Foram relacionadas 17 características com relevância epidemiológica por meio da aplicação de questionários padronizados; também foram realizados testes cutâneos. Foram utilizadas análises univariada e de regressão logística multivariada no exame da associação entre fatores de risco e ocorrência de otite média. RESULTADOS: A otite média revelou forte associação com famílias numerosas, baixo nível educacional dos pais e escolaridade no terceiro ano de vida (p< 0,05); as crianças demonstraram maior suscetibilidade para ocorrência de otite média em presença de asma, tosse, doença do refluxo laringofaríngeo, ronco e apneia (p < 0,05). Alergia e localização urbana aumentaram o risco de otite média em crianças expostas ao fumo em 166% e 277% (p < 0,05), respectivamente; o efeito conjunto de asma e presença de animais de estimação na população alérgica aumentou o risco de recidiva em 11%, enquanto que, em conjunto, alergia, tosse e coriza aumentaram esse risco em 74%. CONCLUSÕES: As infecções de vias aéreas superiores e otite média são doenças pediátricas comuns, fortemente associadas a baixo nível educacional dos pais (p = 0,0001), exposição ao fumo (p = 0,0001), exposição domiciliar ao mofo (p = 0,0001), refluxo laringofaríngeo (p = 0,0002) e ausência de aleitamento materno (p = 0,0014). Também foi observado aumento do risco de recidivas de otite média em presença de alergia, tosse persistente e coriza (p = 0,0001). Deve-se recomendar a modificação dos fatores de risco identificados para otite média, para uma correta intervenção terapêutica primária.