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      Prenatal Exposure to Paint Thinner Alters Postnatal Development and Behavior in Mice

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          Abstract

          Occupational exposure and sniffing of volatile organic solvents continue to be a worldwide health problem, raising the risk for teratogenic sequelae of maternal inhalant abuse. Real life exposures usually involve simultaneous exposures to multiple solvents, and almost all the abused solvents contain a mixture of two or more different volatile compounds. However, several studies examined the teratogenicity due to industrial exposure to a single volatile solvent but investigating the teratogenic potential of complex chemical mixture such as thinner remains unexplored. This study was undertaken to evaluate developmental neurotoxicity of paint thinner using a mouse model. Mated female mice ( N = 21) were, therefore, exposed to repeated and brief inhalation episodes of 0, 300 or 600 ppm of thinner during the entire period of pregnancy. Females weigh was recorded and their standard fertility and reproductive parameters were assessed. After birth postnatal day 1 (PND1), offspring ( N = 88) length and body weight were measured in a daily basis. At PND5, the pups were assessed for their postnatal growth, physical maturation, reflex development, neuromotor abilities, sensory function, activity level, anxiety, depression, learning and memory functions. At adulthood, structural changes of the hippocampus were examined by estimating the total volume of the dentate gyrus. Except one case of thinner induced abortion at the higher dose, our results showed that the prenatal exposure to the solvent did not cause any maternal toxicity or decrease in the viability of the offspring. Therefore, a lower birth weight, decrease in the litter size and delayed reflexes ontogeny were registered in prenatally exposed offspring to both 300 ppm and 600 ppm of thinner. In addition, prenatally exposure to thinner resulted in increased anxiolytic- and depression-like behaviors. In contrast, impaired learning and memory functions and decreased hippocampal dentate gyrus volume were revealed only in the prenatally treated offspring by 600 ppm of thinner. Based on these results, we can conclude that prenatally exposure to paint thinner causes a long-lasting developmental neurotoxicity and alters a wide range of behavioral functions in mice. This shows the risk that mothers who abuse thinner paint expose their offspring.

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          The tail suspension test: a new method for screening antidepressants in mice.

          A novel test procedure for antidepressants was designed in which a mouse is suspended by the tail from a lever, the movements of the animal being recorded. The total duration of the test (6 min) can be divided into periods of agitation and immobility. Several psychotropic drugs were studied: amphetamine, amitriptyline, atropine, desipramine, mianserin, nomifensine and viloxazine. Antidepressant drugs decrease the duration of immobility, as do psychostimulants and atropine. If coupled with measurement of locomotor activity in different conditions, the test can separate the locomotor stimulant doses from antidepressant doses. Diazepam increases the duration of immobility. The main advantages of this procedure are the use of a simple, objective test situation, the concordance of the results with the validated "behavioral despair" test from Porsolt and the sensitivity to a wide range of drug doses.
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            Unusual Repertoire of Vocalizations in the BTBR T+tf/J Mouse Model of Autism

            BTBR T+ tf/J (BTBR) is an inbred mouse strain that displays social abnormalities and repetitive behaviors analogous to the first and third diagnostic symptoms of autism. Here we investigate ultrasonic vocalizations in BTBR, to address the second diagnostic symptom of autism, communication deficits. As compared to the commonly used C57BL/6J (B6) strain, BTBR pups called more loudly and more frequently when separated from their mothers and siblings. Detailed analysis of ten categories of calls revealed an unusual pattern in BTBR as compared to B6. BTBR emitted high levels of harmonics, two-syllable, and composite calls, but minimal numbers of chevron-shaped syllables, upward, downward, and short calls. Because body weights were higher in BTBR than B6 pups, one possible explanation was that larger thoracic size was responsible for the louder calls and different distribution of syllable categories. To test this possibility, we recorded separation calls from FVB/NJ, a strain with body weights similar to BTBR, and 129X1/SvJ, a strain with body weights similar to B6. BTBR remained the outlier on number of calls, displaying low numbers of complex, upward, chevron, short, and frequency steps calls, along with high harmonics and composites. Further, developmental milestones and growth rates were accelerated in BTBR, indicating an unusual neurodevelopmental trajectory. Overall, our findings demonstrate strain-specific patterns of ultrasonic calls that may represent different lexicons, or innate variations in complex vocal repertoires, in genetically distinct strains of mice. Particularly intriguing is the unusual pattern of vocalizations and the more frequent, loud harmonics evident in the BTBR mouse model of autism that may resemble the atypical vocalizations seen in some autistic infants.
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              Postnatal development of locomotion in the laboratory rat.

              In laboratory rats (Rattus norvegicus) aged 1 to 21 days emergence of postural and locomotor skills was studied in the open field and in experimental situations with homing used as motivation. Righting is mediated initially by curving and rocking of the trunk, later head and shoulder are rotated, and lastly the hindlimbs turn and provide co-ordinated support. Pivoting prodominates during the second half of the first week, crawling during most of the second week, and walking or running by the end of the second week. Balancing on narrow paths and compensating for lateral displacement on rotating rods mature later, as do various skills (climbing up or down on inclined surfaces, rods and ropes, and jumping across gaps) that require substantial hindlimb co-ordiantion.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                11 September 2017
                2017
                : 11
                : 171
                Affiliations
                [1]Laboratory of Pharmacology, Neurobiology and Behavior (URAC-37), Faculty of Sciences Semlalia, University Cadi Ayyad Marrakech, Morocco
                Author notes

                Edited by: Nilesh Bhailalbhai Patel, University of Nairobi, Kenya

                Reviewed by: Noriyuki Koibuchi, Gunma University, Japan; Valerie J. Bolivar, Wadsworth Center, United States

                *Correspondence: Saadia Ba-M’hamed bamhamed@ 123456uca.ma

                These authors have contributed equally to this work.

                Article
                10.3389/fnbeh.2017.00171
                5604056
                bafa5ff0-dee3-48c0-a177-b08708c2dc90
                Copyright © 2017 Malloul, Mahdani, Bennis and Ba-M’hamed.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 June 2017
                : 29 August 2017
                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 91, Pages: 16, Words: 12431
                Categories
                Neuroscience
                Original Research

                Neurosciences
                paint thinner,prenatal exposure,fertility,reproduction,development,behavior
                Neurosciences
                paint thinner, prenatal exposure, fertility, reproduction, development, behavior

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