Absence of preference for social novelty and increased grooming in integrin ß3 knockout mice: initial studies and future directions.

Elevated whole blood serotonin 5-HT, or hyperserotonemia, is a common biomarker in autism spectrum disorder (ASD). The integrin ß3 receptor subunit gene (ITGB3) is a quantitative trait locus for whole blood 5-HT levels. Recent work shows that integrin ß3 interacts with the serotonin transporter (SERT) in both platelets and in the midbrain. Furthermore, multiple studies have now reported gene-gene interaction between the integrin ß3 and SERT genes in association with ASD. Given the lack of previous data on the impact of integrin ß3 on brain or behavioral phenotypes, we sought to compare mice with decreased or absent expression of the integrin ß3 receptor subunit (Itgb3 +/- and -/-) with wildtype littermate controls in behavioral tasks relevant to ASD. These mice did not show deficits in activity level in the open field or anxiety-like behavior on the elevated plus maze, two potential confounds in the evaluation of mouse social behavior. In the three-chamber social test, mice lacking integrin ß3 were shown to have normal sociability but did not show a preference for social novelty. Importantly, the absence of integrin ß3 did not impair olfaction or the ability to recall familiar social odors. Additionally, mice lacking integrin ß3 showed increased grooming behavior in novel environments. These preliminary studies reveal altered social and repetitive behavior in these mice, which suggests that the integrin ß3 subunit may be involved in brain systems relevant to ASD. Further work is needed to fully characterize these behavioral changes and the underlying brain mechanisms.

The acute impact of ethanol on cognitive performance in rhesus macaques.

Decreased cognitive control over prepotent responses has been hypothesized to contribute to ethanol-induced behavioral disinhibition. However, the effects of ethanol on specific cognitive domains associated with decision making have not been extensively studied. We examined the impact of acute ethanol administration on cognitive performance of nonhuman primates. Studies were conducted using 0.2, 0.5, and 1 g/kg intravenous ethanol in rhesus macaques performing touch screen-based tasks examining stimulus discrimination, stimulus reversal, and stimulus response performance. The impact on attentional processing was also evaluated. Ethanol reduced the accuracy of reversal performance marginally at 0.2 g/kg and significantly at 0.5 g/kg. This effect was selective given an absence of impairment on the stimulus discrimination and stimulus response tasks at these doses. Performance on stimulus discrimination was impaired at 1.0 g/kg, which prevented determination of reversal performance. Analysis of post-error response times demonstrated that error processing was impaired at both 0.2 and 0.5 g/kg. Ethanol also increased the number of omissions and delayed responses on an attentional task, suggesting more frequent attentional lapses. These data demonstrate that cognitive function mediated by specific prefrontal cortical brain regions is particularly sensitive to ethanol and suggest specific cognitive mechanisms that may underlie harmful decisions made at low doses of ethanol.