d-Cycloserine improves the impaired sociability of the Balb/c mouse

Impaired Sociability of the Balb/c Mouse, an Animal Model of Autism Spectrum Disorders, is Attenuated by NMDA Receptor Agonist Interventions: Clinical Implications

“…Thus, the integrity of circuits necessary for normal cognition and social behavior, whose nodes include cerebral cortex, anterior cingulate gyrus, hippocampus, and amygdala, among other discrete anatomic brain regions, contain NMDA receptors (Benes, 2010). An emerging body of preclinical and clinical data suggests that NMDA receptor hypofunction at the level of the receptor itself or due to abnormalities upstream or downstream of the receptor contributes to both cognitive problems and impaired sociability (Darrah et al, 2008;Deutsch et al, 2011;Halene et al, 2009;Jacome et al, 2011b;Labrie et al, 2008). The ability of glycine to make glutamate a more efficient neurotransmitter and, thereby, increase the likelihood the channel will transiently assume an open configuration and allow calcium ions to flux freely has aroused interest in the strychnine-insensitive o b l i g a t o r y g l y c i n e c o -a g o n i s t b i n d i n g s i t e o n t h e N M D A r e c e p t o r a s a t a r g e t f o r medication development to address presumptive NMDA receptor hypofunction.…”

“…Impaired sociability is a domain of psychopathology that contributes significantly to the functional disability and poor quality of life of persons with Autism Spectrum Disorders (ASDs) (Brodkin, 2007;Crawley, 2004Crawley, , 2007Deutsch et al, 2011). Although cognitive functioning may influence the expression of impaired sociability, the relationship between cognitive deficits and impaired sociability is not a linear one; thus, for example, persons with ASDs whose IQs are in the near-normal to above normal range may manifest profound deficits of sociability that are similar to those shown by persons with ASDs and intellectual disability (Noterdaeme et al, 2010).…”

“…In any event, the Balb/c mouse strain, like the targeted genetic mutant mouse strains described above, shows quantitative deficits of sociability in a standard mouse paradigm (Burket et al, 2010b;Brodkin, 2007;Moy et al, 2007;Sankoorikal et al, 2006). These deficits of sociability are observable when Balb/c mice are in the presence of a salient social stimulus mouse that is either enclosed or allowed to interact freely with a Balb/c mouse (Burket et al, 2010b; www.intechopen.com Impaired Sociability of the Balb/c Mouse, an Animal Model of Autism Spectrum Disorders, is Attenuated by NMDA Receptor Agonist Interventions: Clinical Implications 325 Deutsch et al, 2011;Jacome et al, 2011a,b, in press). Specifically, Balb/c mice make fewer discrete episodes of social approach and spend less time exploring (sniffing) and in the vicinity of an enclosed and freely-moving social stimulus mouse (Jacome et al, 2011;Brodkin, 2007).…”

“…These deficits of sociability are observable when Balb/c mice are in the presence of a salient social stimulus mouse that is either enclosed or allowed to interact freely with a Balb/c mouse (Burket et al, 2010b; www.intechopen.com Impaired Sociability of the Balb/c Mouse, an Animal Model of Autism Spectrum Disorders, is Attenuated by NMDA Receptor Agonist Interventions: Clinical Implications 325 Deutsch et al, 2011;Jacome et al, 2011a,b, in press). Specifically, Balb/c mice make fewer discrete episodes of social approach and spend less time exploring (sniffing) and in the vicinity of an enclosed and freely-moving social stimulus mouse (Jacome et al, 2011;Brodkin, 2007). Quite remarkably, D-cycloserine, a partial glycine agonist for the obligatory co-agonist binding site, and D-serine, a full agonist for this site that may also be the endogenous ligand, were able to attenuate the severity of the Balb/c mouse's deficits of sociability (Deutsch et al, 2011;Jacome et al, 2011a,b).…”

“…Specifically, Balb/c mice make fewer discrete episodes of social approach and spend less time exploring (sniffing) and in the vicinity of an enclosed and freely-moving social stimulus mouse (Jacome et al, 2011;Brodkin, 2007). Quite remarkably, D-cycloserine, a partial glycine agonist for the obligatory co-agonist binding site, and D-serine, a full agonist for this site that may also be the endogenous ligand, were able to attenuate the severity of the Balb/c mouse's deficits of sociability (Deutsch et al, 2011;Jacome et al, 2011a,b). These effects of NMDA receptor agonist interventions may be due to direct effects on the sociability deficit itself, as opposed to nonspecific effects resulting from increased locomotor activity in general.…”