Increased volumes of lobule VI in a valproic acid model of autism are associated with worse set-shifting performance in male Long-Evan rats.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a skewed sex-based diagnostic ratio. While males are at a higher risk for ASD, it is critical to understand the neurobiology of the disorder to develop better treatments for both males and females. Our prior work has demonstrated that VPA (valproic acid) treated offspring had impaired performance on an attentional set-shifting task. The current study used MRI and regions of interest analyses to measure the volumes of cerebellar subregions in VPA and controls rats that had participated in the attentional set-shifting task. VPA males had significantly more volume in lobule VI compared to male controls. VPA female rats had significantly less volume in lobules I, IV and X compared to female controls. In addition, it was revealed that decreases in volume for VPA females was associated with worse performance. Males with increases in lobule VI were also impaired on the set-shifting task. Similar volumetric differences within the cerebellum have been observed in humans with ASD, which suggests that the VPA model is capturing some of the same brain changes observed in humans with ASD, and that these changes in volume may be impacting cognition.

Valproic acid treated female Long-Evans rats are impaired on attentional set-shifting.

Autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by social deficits, communication impairments, restrictive behaviors, and cognitive flexibility deficits. The valproic acid (VPA) model of autism has been widely used to examine changes in rodent behavior and neurobiology to better understand ASD. This study examined social and anxiety behavior as well as cognitive flexibility in VPA and control offspring. Results for social behavior were consistent with prior studies showing reduced sociability in VPA rats and increased self-grooming, which may be viewed as a repetitive behavior. VPA rats also had deficits in performing the set-shifting task, with female VPA rats demonstrating greater impairment compared to female control rats and male VPA rats. These results support the hypothesis that females diagnosed with ASD may suffer from different symptoms and present a unique behavioral profile compared to males with ASD. Female VPA rats were also less likely to form an attentional set; offering evidence that the VPA model of autism is encompassing executive function deficits similar to those observed in humans with ASD.

Effects of cannabinoid administration for pain: A meta-analysis and meta-regression.

Chronic pain states have resulted in an overreliance on opioid pain relievers, which can carry significant risks when used long term. As such, alternative pain treatments are increasingly desired. Although emerging research suggests that cannabinoids have therapeutic potential regarding pain, results from studies across pain populations have been inconsistent. To provide meta-analytic clarification regarding cannabis's impact on subjective pain, we identified studies that assessed drug-induced pain modulations under cannabinoid and corresponding placebo conditions. A literature search yielded 25 peer-reviewed records that underwent data extraction. Baseline and end-point data were used to compute standardized effect size estimates (Cohen's d) across cannabinoid administrations (k = 39) and placebo administrations (k = 26). Standardized effects were inverse-variance weighted and pooled across studies for meta-analytic comparison. Results revealed that cannabinoid administration produced a medium-to-large effect across included studies, Cohen's d = -0.58, 95% confidence interval (CI) [-0.74, -0.43], while placebo administration produced a small-to-medium effect, Cohen's d = -0.39, 95% CI [-0.52, -0.26]. Meta-regression revealed that cannabinoids, ß = -0.43, 95% CI [-0.62, -0.24], p < .05, synthetic cannabinoids, ß = -0.39, 95% CI [-0.65, -0.14], p < .05, and sample size, ß = 0.01, 95% CI [0.00, 0.01], p < .05, were associated with marked pain reduction. These outcomes suggest that cannabinoid-based pharmacotherapies may serve as effective replacement/adjunctive options regarding pain, however, additional research is warranted. Additionally, given demonstrated neurocognitive side effects associated with some constituent cannabinoids (i.e., THC), subsequent work may consider developing novel therapeutic agents that capitalize on cannabis's analgesic properties without producing adverse effects. (PsycINFO Database Record (c) 2019 APA, all rights reserved).