Improved Social Interaction and Cognition in Mouse Models of Autism Spectrum Disorder

Growing knowledge about genetic mutations in people with autism is enabling researchers to evaluate hypothesis-driven pharmacological interventions for their ability to reverse the biological and behavioral consequence of specific mutations that cause autism. One of the genes in the 16p11.2 deletion region regulates the inhibitory neurotransmitter GABA. Researchers tested the hypothesis that increasing GABA neurotransmission using R-baclofen, which binds to GABA-B receptors, could reverse analogous behavioral symptoms in a mouse model of 16p11.2 deletion syndrome.

 In the current paper, researchers report the results of animal model studies using two independently derived lines of mutant mice, each missing a chromosomal region analogous to human 16p11.2. Normal and mutant mice at both labs were tested after receiving R-baclofen in their drinking water on three tasks: novel object recognition, object location memory, and contextual recognition learning and memory. In addition, R-baclofen treated mutant mice scored better after treatment on each cognitive task than the untreated mutant mice. R-baclofen also increased scores on a standard assay of mouse social behaviors — male-female reciprocal social interactions — in the 16p11.2 mutant mice.

This study suggests that R-baclofen should be explored for the treatment of cognitive phenotypes in affected humans.