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      Adolescent Opiate Exposure in the Female Rat Induces Subtle Alterations in Maternal Care and Transgenerational Effects on Play Behavior

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          Abstract

          The non-medical use of prescription opiates, such as Vicodin ® and MSContin ®, has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females’ spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1) demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e., social grooming and social exploration). Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal–offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

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          Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat.

          The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased alpha2 adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to "program" behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.
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            Variations in maternal care in the rat as a mediating influence for the effects of environment on development.

            Variations in maternal care have been widely considered as a critical influence in development. In the rat, variations in maternal behavior, particularly in licking/grooming, regulate the development of endocrine, emotional and cognitive responses to stress. These studies form the basis of a potentially useful model for the study of maternal effects in mammals. In this paper we provide a detailed methodological investigation into this model of maternal behavior, providing an analysis of the frequency, temporal dynamics, and transmission of maternal licking/grooming in several large cohorts. Frequency data indicate that licking/grooming is normally distributed across dams. The peak in licking/grooming occurs in the first few days postpartum and gradually declines. Dams designated as High or Low LG mothers differ in this behavior only during the first week postpartum. Observations over Days 2 to 5 postpartum are essential for the reliable assessments of individual differences in maternal behavior. Individual differences in licking/grooming behavior are stable across multiple litters, and are not associated with differences in litter size, weaning weight of pups, or gender ratio of the litter. We also observed no significant differences in the amount of licking/grooming received by individual pups within a litter, though variation does exist. Finally, maternal licking/grooming is transmitted to female offspring, though there is considerable within-litter variation in the expression of this behavior. Overall, these findings indicate considerable, normal variations in licking/grooming in the rat that are a stable, individual characteristic of rat dams.
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              Maternal care, hippocampal synaptogenesis and cognitive development in rats.

              We report that variations in maternal care in the rat promote hippocampal synaptogenesis and spatial learning and memory through systems known to mediate experience-dependent neural development. Thus, the offspring of mothers that show high levels of pup licking and grooming and arched-back nursing showed increased expression of NMDA receptor subunit and brain-derived neurotrophic factor (BDNF) mRNA, increased cholinergic innervation of the hippocampus and enhanced spatial learning and memory. A cross-fostering study provided evidence for a direct relationship between maternal behavior and hippocampal development, although not all neonates were equally sensitive to variations in maternal care.
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                Author and article information

                Journal
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Research Foundation
                1664-0640
                19 March 2011
                06 June 2011
                2011
                : 2
                : 29
                Affiliations
                [1] 1simpleDepartment of Biomedical Science, Cummings School of Veterinary Medicine, Tufts University North Grafton, MA, USA
                Author notes

                Edited by: Josephine Johns, University of North Carolina at Chapel Hill, USA

                Reviewed by: Rina Eiden, University at Buffalo, USA; Craig H. Kinsley, University of Richmond, USA

                *Correspondence: Elizabeth M. Byrnes, Section of Neuroscience and Reproductive Biology, Department of Biomedical Science, Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA 01536, USA. e-mail: elizabeth.byrnes@ 123456tufts.edu

                This article was submitted to Frontiers in Child and Neurodevelopmental Psychiatry, a specialty of Frontiers in Psychiatry.

                Article
                10.3389/fpsyt.2011.00029
                3112319
                21713113
                f2930ae3-3dce-48ac-9630-ed974f725869
                Copyright © 2011 Johnson, Carini, Schenk, Stewart and Byrnes.

                This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

                History
                : 25 February 2011
                : 08 May 2011
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 98, Pages: 10, Words: 8984
                Categories
                Psychiatry
                Original Research

                Clinical Psychology & Psychiatry
                nursing,maternal attachment,offspring,rough and tumble play,morphine

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