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Item does not contain fulltext Serotonin is well known for its role in psychiatric disorders like depression and autism, but it is less clear how aberrant behaviour associated with these disorders are shaped by serotonergic alterations during prenatal and postnatal development. The use of serotonergic antidepressant agents and other drugs during pregnancy and breastfeeding can change brain development, and the behavioural consequences may depend on the stage of development; prenatal, early and late postnatal. The aim of this review is to provide an overview of the behavioural consequences of changes in serotonin levels during these three critical developmental stages. The studies together demonstrate that risk for mood disorders (including social deficits) is related to serotonergic perturbations during the prenatal and postnatal phases, whereas risk for autism-like features and sexual abnormalities increases when serotonin levels are increased during the postnatal period. This insight may inform timed strategies to reduce risk for psychiatric disorders.

Item does not contain fulltext Rodent behavioural tasks are indispensable to advance the understanding of gene x environment interactions in neuropsychiatric disorders and the discovery of new therapeutic strategies. Yet, the actual translation of rodent data to humans, and thereby the understanding of the pathophysiology of neuropsychiatric disorders is limited. The main reason for the translational flaw is that many behavioural tasks for rodents are based on face or predictive validity, whereas these types of validity often lack a pathophysiological basis. Furthermore, many behavioural tasks for rodents do not implement human task parameters or use task parameters in a controlled manner, whereas they are parameters that provide the environmental challenges to test gene function. The aim of this perspective is to address the status quo of behavioural tasks for rodents, their limitations and their strengths, and the reasons why they could lead to suboptimal translational research. I also suggest an approach to come closer to neuropsychiatric behavioural tasks for rodents, namely a more careful implementation of human task parameters and subdivision of behaviour into perceptional, motivational, activational and switching domains. Finally, I will touch upon behavioural tasks for rodents that are currently lacking and needed to catch up neuropsychiatric research.

Contains fulltext : 169896.pdf (Publisher’s version ) (Closed access) Anxiety as a common feature of several neurodegenerative/polyglutamine diseases is an important aspect for the face validity of an animal model for Spinocerebellar Ataxia type 17 (SCA17). Risk assessment and anxiety-like traits were characterised in 3-6-9 months old rats of a transgenic model for SCA17 using the standard behavioural test elevated plus maze. In addition, c-Fos immunostainings in the basolateral amygdala evaluated neuronal activation in correlation to the behavioural responses. The most prominent behavioural effect was a higher level of risk assessment in the transgenic rats. In addition, an increase in anxiety-related behaviour in these rats was found. Although the EPM caused no overall effect on c-Fos expression, a negative correlation with the anxiety-like behavioural response was observed. Our results suggest that the SCA17 rat model displays an anxious phenotype already at 3 months of age resembling the generalized anxiety in early symptomatic SCA17 patients, thus confirming the validity of this rat model.

Item does not contain fulltext It has been observed that men and women show performance differences in the Iowa Gambling Task (IGT), a task of decision-making in which subjects through exploration learn to differentiate long-term advantageous from long-term disadvantageous decks of cards: men choose more cards from the long-term advantageous decks than women within the standard number of 100 trials. Here, we aim at discussing psychological mechanisms and neurobiological substrates underlying sex differences in IGT-like decision-making. Our review suggests that women focus on both win-loss frequencies and long-term pay-off of decks, while men focus on long-term pay-off. Furthermore, women may be more sensitive to occasional losses in the long-term advantageous decks than men. As a consequence hereof, women need 40-60 trials in addition before they reach the same level of performance as men. These performance differences are related to differences in activity in the orbitofrontal cortex and dorsolateral prefrontal cortex as well as in serotonergic activity and left-right hemispheric activity. Sex differences in orbitofrontal cortex activity may be due to organisational effects of gonadal hormones early in life. The behavioural and neurobiological differences in the IGT between men and women are an expression of more general sex differences in the regulation of emotions. We discuss these findings in the context of sex differences in information processing related to evolutionary processes. Furthermore we discuss the relationship between these findings and real world decision-making.

Contains fulltext : 96334.pdf (Publisher’s version ) (Closed access) A well-known example for gene x environment interactions in psychiatry is the one involving the low activity (s) allelic variant of the serotonin transporter (5-HTT) promoter polymorphism (5-HTTLPR) that in the context of stress increases risk for depression. In analogy, 5-HTT knockout rodents are highly responsive to early life, but also adult external stressors, albeit conflicting data have been obtained. In our study on emotion and cognition using homozygous 5-HTT knockout (5-HTT(-/-)) and wild-type (5-HTT(+/+)) rats we have been confronted with animal facility construction, which were associated with severe lifetime stress (noise and vibrations). To assess the impact of construction stress on well-established 5-HTT(-/-) rat phenotypes we conducted ad hoc analyses of 5-HTT(-/-) and 5-HTT(+/+) rats that grew up before and during the construction. The reproductive capacity of the parents of the experimental 5-HTT(+/-) rats was significantly decreased. Further, 5-HTT(-/-) anxiety-related phenotypes in the elevated plus maze and social interaction tests were abolished after construction noise exposure, due to increased anxiety in 5-HTT(+/+) rats and decreased anxiety in 5-HTT(-/-) rats (social interaction test only). In addition, reversal learning was improved in 5-HTT(+/+) and, to a milder extent, decreased in 5-HTT(-/-) rats. Finally, construction stress genotype-independently increased behavioural despair in the forced swim test. In conclusion, severe construction stress induces 5-HTT genotype-dependent 'for-better-and-for-worse' effects. These data importantly contribute to the understanding of 5-HTT gene x environment interactions and show the risk of losing genotype effects by construction stress.

orrigendum orrigendum to “Serotonin transporter genotype × construction stress nteraction in rats” [Behav. Brain Res. 223 (2011) 169–175] ieter Schippera,b, Lourens J.P. Nonkesb, Peter Karelb, Amanda J. Kiliaana,b, Judith R. Hombergb,∗ Department of Anatomy, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands