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As one of the leading causes of death and serious illnesses, tobacco smoking remains a significant issue in modern societies. Many individuals smoke during adolescence, a trend that has been exacerbated by the prevalence of vaping among young people. In this context, studying the behavioral effects induced by nicotine administration in male and female rats, during the adolescent period, assumes great importance because it can help to better understand the dynamics underlying tobacco use in the two sexes. For this purpose, we employed 4 groups of rats, 2 male and 2 female groups, chronically treated with saline or nicotine 3 mg/kg i.p. for 30 days, spanning from postnatal day 30 to postnatal day 60. Utilizing quantitative analyses and T-pattern detection and analysis, our findings revealed a complex and multifaceted behavioral reorganization in adolescent rats subjected to chronic nicotine administration. Specifically, we observed an increase of anxiety in males and a reduction in females. The distinctive structural changes, induced by chronic nicotine in both sexes, have significant implications, from a translational perspective, for studies on nicotine dependence disorders., Competing Interests: Declaration of competing interest All the Authors of the above-mentioned manuscript, submitted to Progress in Neuropsychopharmacology & Biological Psychiatry on February 6th 2024, declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Tobacco smoking is a serious health problem worldwide and a leading cause of mortality. Nicotine, the addictive component of tobacco, affects a range of emotional responses, including anxiety-related behaviors. Although perceived by smokers to be anxiolytic, evidence suggests that smoking increases anxiety and that mood fluctuates with nicotine intake. Thus, nicotine addiction may depend on easing the psychobiological distress caused by its abuse. The lateral habenula (LHb) has been implicated as a neural substrate for acute nicotine-induced anxiety, but its role in anxiety-like behaviors associated with chronic nicotine exposure has not been explored. Here, we assessed the effect of chronic nicotine exposure and its subsequent overnight withdrawal on anxiety-like behavior using both quantitative and multivariate T-pattern analysis in rats tested using the hole-board apparatus. Additionally, we explored the role of the LHb by comparing the behavioral effects of short-term nicotine withdrawal in chronically treated LHb-lesioned rats. Quantitative analysis revealed increased anxiety-like behavior in chronically treated overnight nicotine-deprived rats, as manifested in reduced general and focused exploratory behaviors, which was eased in animals that received nicotine. Quantitative analysis failed to reveal a role of the LHb in overnight nicotine deprivation-induced anxiety. Conversely, T-pattern analysis of behavioral outcomes revealed that chronic nicotine-treated rats still show anxiety-like behavior following nicotine challenge. Moreover, it demonstrated that the LHb lesion induced a stronger anxiolytic-like response to the acute challenge of nicotine in chronically nicotine-exposed animals, implicating the LHb in the anxiogenic effect of chronic nicotine exposure. These data further highlight the LHb as a promising target for smoking cessation therapies and support the importance of T-pattern analysis for behavioral analysis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The present study aimed to assess the behavioral effects of chronic treatments of different doses of nicotine by using both quantitative and multivariate T-pattern analysis (TPA), which can reveal hidden behavioral structures, in Sprague-Dawley rats tested in the hole-board apparatus. To this purpose, nicotine ditartrate was administered at the doses of 0.1, 0.5 and 1 mg/kg i.p., three times per day, for 14 consecutive days. As to quantitative evaluations, we observed significant reductions in the mean durations and mean frequencies of walking, climbing, immobile-sniffing and rearing in comparison to control. A significant reduction of edge-sniff and head-dip mean frequencies was also detected for all the doses tested. TPA revealed an increase in the number and the mean length of different T-patterns induced by the three doses of nicotine. On the other hand, a significant reduction of the mean occurrences of T-patterns was revealed. Overall, our results obtained by using both quantitative and T-pattern analyses indicate that chronic nicotine induces an anxiety condition characterized by a behavioral re-organization orbiting around the two main components of hole exploration, that is, head-dip and edge-sniff. A better understanding of the link between nicotine and anxiety might help to find new therapies for smoking cessation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate quality of life (QoL) and its possible determinants in patients affected by Duchenne muscular dystrophy (DMD) in late stages of their disease, when non-invasive ventilation (NIV) is already established. Forty-eight DMD patients who were treated by NIV were enrolled. QoL was assessed by the Individualized Neuromuscular Quality of Life (INQoL) questionnaire. By this questionnaire, different aspects of QoL were assessed on a scale from 0 (best) to 100 (worst). In addition, motor and respiratory function tests were performed. Dysautonomia symptoms, sleep quality, sleepiness, anxiety, and depression were evaluated by validated questionnaires. The global INQoL score was 42.8 ± 19, reflecting a moderately altered QoL. The physical health domain was heavily impaired while the psychosocial domain was only mildly affected. Independence had the highest scores (81.1 ± 21.2), proving to be the most affected item. On multivariate analysis, maximal inspiratory pressure and Pittsburgh Sleep Quality Index, but not daily duration of NIV therapy, predicted global INQoL score. Respiratory impairment and sleep quality were independent predictors of poor QoL in DMD patients under NIV. Sleep quality in DMD is often disregarded, while it should be carefully addressed to ensure a better QoL., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Markers of histaminergic dysregulation were found in several neuropsychiatric disorders characterized by repetitive behaviours, thoughts and stereotypies. We analysed the effect of acute histamine depletion by means of i. c.v. injections of alpha-fluoromethylhistidine, a blocker of histidine decarboxylase, on the temporal organization of motor sequences of CD1 mice behaviour in the open-field test. An ethogram encompassing 9 behavioural components was employed. Durations and frequencies were only slightly affected by treatments. However, as revealed by multivariate t-pattern analysis, histamine depletion was associated with a striking increase in the number of behavioural patterns. We found 42 patterns of different composition occurring, on average, 520.90 ± 50.23 times per mouse in the histamine depleted (HD) group, whereas controls showed 12 different patterns occurring on average 223.30 ± 20.64 times. Exploratory and grooming behaviours clustered separately, and the increased pattern complexity involved exclusively exploratory patterns. To test the hypothesis of a histamine-dopamine interplay on behavioural pattern phenotype, non-sedative doses of the D2/D3 antagonist sulpiride (12.5-25-50 mg/kg) were additionally administered to different groups of HD mice. Sulpiride counterbalanced the enhancement of exploratory patterns of different composition, but it did not affect the mean number of patterns at none of the doses used. Our results provide new insights on the role of histamine on repetitive behavioural sequences of freely moving mice. Histamine deficiency is correlated with a general enhancement of pattern complexity. This study supports a putative involvement of histamine in the pathophysiology of tics and related disorders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In patients with late-onset Pompe disease, we explored the role of the Cardiopulmonary Exercise Test (CPET) and the Six-Minute Walking Test (6MWT) in the assessment of exercise capacity and in the evaluation of the effects of enzyme replacement therapy (ERT). Eight patients affected by late-onset Pompe disease, followed up at the Centre for Neuromuscular Diseases and treated with ERT, underwent a baseline evaluation with a spirometry, a CPET and a 6MWT. Four of them were restudied after 36 months of treatment. Three patients showed a reduction in exercise capacity as evaluated by peak oxygen uptake (VO2) measured at the CPET and Distance Walked (DW) measured at the 6MWT (median % predicted: 67.1 [range 54.3-99.6] and 67.3 [56.6-82.6], respectively). Cardiac and respiratory limitations revealed by the CPET were correlated to peak VO2, but not to the DW. Nevertheless, percent of predicted values of peak VO2 and DW were strongly correlated (rho = 0.85, p = 0.006), and close to identity. In the longitudinal evaluation forced vital capacity decreased, while peak VO2 and DW showed a trend to a parallel improvement. We concluded that although only the CPET revealed causes of exercise limitation, which partially differed among patients, CPET and 6MWT showed a similar overall degree of exercise impairment. That held true in the longitudinal assessment during ERT, where both tests demonstrated similar small improvements, occurring despite deterioration in forced vital capacity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The aim of the present study was to evaluate, by means of quantitative and multivariate analyses, the effects of diazepam on the behavioral structure of the rat's response to pain in the hot-plate test as well as whether such changes are associated with drug-induced effects on anxiety and/or nociception. To this purpose, ten groups of male Wistar rats were intraperitoneally injected with saline, diazepam (0.25, 0.5 and 2 mg/kg), FG-7142 (1, 4 and 8 mg/kg) or morphine (3, 6 and 12 mg/kg). The mean number and mean latency to first appearance were calculated for each behavioral component. In addition, multivariate cluster and adjusted residual analyses based on the elaboration of transition matrices were performed. Three main behavioral categories were identified: exploratory (walking, sniffing), primary noxious-evoked (hind paw licking, front paw licking, shaking/stamping) and escape (climbing, jumping). Although no significant modifications in the latencies of the primary noxious-evoked components were induced by treatment with diazepam or FG-7142, significant effects were provoked by morphine treatment. Multivariate analyses showed that diazepam-induced anxiolysis redirected the rat's behavior toward a more purposeful and effective escape strategy. In contrast, the high level of anxiety induced by FG-7142 caused the behavioral structure to become disorganized and not purposefully oriented. Changes in the organization of behavioral components were observed in morphine-treated animals and mainly consisted of modifications in the primary noxious-evoked and escape components. The findings suggest that the effects of diazepam on the structure of the rat's response to pain in the hot-plate test are more likely attributable to anxiolysis than pain modulation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)