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Social behavior abnormalities in Fragile X syndrome (FXS) are characterized by social withdrawal, anxiety, and deficits in social cognition. To assess these deficits, a model of FXS, the Fmr1 knockout mouse (Fmr1 KO), has been utilized. This mouse model has a null mutation in the fragile X mental retardation 1 gene (Fmr1) and displays physical and behavioral characteristics similar to humans with FXS. Several studies have investigated the social behavior of this model, but the results on the behavioral phenotype have not been consistent. In order to further characterize the social behavior in the knockout, isolation-reared Fmr1 KO were evaluated to determine if they differ in their social behavior compared to wild-type littermate controls. Differences by genotype were not observed in social approach behavior; however, the knockout mice showed a significantly reduced preference for social novelty and decreased sniff time in the sociability phase. These findings add to the growing body of knowledge on the subtle differences in social behavior shown by the Fmr1 knockout mice, and that differences occur when the subjects are isolation-reared. Validity of the model and possible changes to methodology are discussed. Keywords Fragile X syndrome * fmrl knockout mouse * Social behavior, Introduction Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism (Cohen et al. 2005; Hagerman and Hagerman 2002). The disorder is caused by a [...]

Abstract: The neurotransmitter acetylcholine is an important modulator of cognitive functions including attention, learning, and memory. The actions of acetylcholine are mediated by five distinct muscarinic acetylcholine receptor subtypes (M1–M5). The lack of drugs with a high degree of selectivity for these subtypes has impeded the determination of which subtypes mediate which components of cholinergic neurotransmission relevant to cognitive abilities. The present study examined the behavioral functions of the M2 muscarinic receptor subtype by utilizing congenic C57BL/6 mice possessing a null-mutation in the M2 muscarinic receptor gene (M2 −/− mice). Comprehensive assessment of general health and the neurological function found no major differences between M2 −/− and wild-type (M2 +/+) mice. In the tests of learning and memory, M2 −/− mice were impaired in the acquisition (trials to criterion), but not the retention (72h) of a passive avoidance task. In a novel open field, M2 −/− mice were impaired in between-sessions, but not within-session habituation. In a holeboard test of spatial memory, M2 −/− mice committed more errors in working memory than M2 +/+ mice. Reference memory did not differ between the genotypes. M2 −/− mice showed no impairments in either cued or contextual fear conditioning. These findings replicate and extend earlier findings in a hybrid strain and solidify the interpretation that the M2 receptor plays a critical role in specific components of cognitive abilities. [Copyright &y& Elsevier]

Galanin is a 29 or 30 amino acid peptide with a close anatomical and neurophysiological relationship with neural systems mediating stress. In rodent behavioral studies, the consequences of galanin activity on stress-related behaviors such as anxiety-like and depression-like behavior varies according to site of administration and behavioral assay used. However, galaninergic systems remain a promising novel target for new antianxiety and antidepressant drugs. Current work attempting to delineate which galanin receptor subtypes mediate which effects of galanin will undoubtedly inform the development of these drugs. Further, the well-established deleterious effects of galanin on cognitive function provide support for galanin as a novel link between stress, anxiety and memory. This link suggests that galaninergic drugs could provide a novel therapeutic option for psychopathologies, such as post-traumatic stress syndrome, in which abnormal memory and emotion are intertwined., ((c) 2006 Prous Science. All rights reserved.)