R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice

Laura J. Stoppel, Tatiana M. Kazdoba, Melanie D. Schaffler, Anthony R. Preza, Arnold Heynen, Jacqueline Crawley, Mark F. Bear

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Human chromosome 16p11.2 microdeletion is among the most common gene copy number variations (CNVs) known to confer risk for intellectual disability (ID) and autism spectrum disorder (ASD) and affects an estimated 3 in 10 000 people. Caused by a single copy deletion of ∼27 genes, 16p11.2 microdeletion syndrome is characterized by ID, impaired language, communication and socialization skills, and ASD. Studies in animal models where a single copy of the syntenic 16p11.2 region has been deleted have revealed morphological, behavioral, and electrophysiological abnormalities. Previous studies suggested the possibility of some overlap in the mechanisms of pathophysiology in 16p11.2 microdeletion syndrome and fragile X syndrome. Improvements in fragile X phenotypes have been observed following chronic treatment with R-baclofen, a selective agonist of GABA B receptors. We were therefore motivated to investigate the effects of chronic oral R-baclofen administration in two independently generated mouse models of 16p11.2 microdeletion syndrome. In studies performed across two independent laboratories, we found that chronic activation of GABA B receptors improved performance on a series of cognitive and social tasks known to be impaired in two different 16p11.2 deletion mouse models. Our findings suggest that R-baclofen may have clinical utility for some of the core symptoms of human 16p11.2 microdeletion syndrome.

Original languageEnglish (US)
Pages (from-to)513-524
Number of pages12
JournalNeuropsychopharmacology
Volume43
Issue number3
DOIs
StatePublished - Feb 1 2018

Fingerprint

Baclofen
Interpersonal Relations
Intellectual Disability
GABA-B Receptor Agonists
GABA-B Receptors
Fragile X Syndrome
Gene Dosage
Socialization
Gene Deletion
Human Chromosomes
Language
Animal Models
Communication
Phenotype
Autism Spectrum Disorder
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice. / Stoppel, Laura J.; Kazdoba, Tatiana M.; Schaffler, Melanie D.; Preza, Anthony R.; Heynen, Arnold; Crawley, Jacqueline; Bear, Mark F.

In: Neuropsychopharmacology, Vol. 43, No. 3, 01.02.2018, p. 513-524.

Research output: Contribution to journalArticle

Stoppel, Laura J. ; Kazdoba, Tatiana M. ; Schaffler, Melanie D. ; Preza, Anthony R. ; Heynen, Arnold ; Crawley, Jacqueline ; Bear, Mark F. / R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice. In: Neuropsychopharmacology. 2018 ; Vol. 43, No. 3. pp. 513-524.
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