Mutations in contactin-associated protein-like 2 (CNTNAP2) cause cortical dysplasia and focal epilepsy syndrome. The knockout of the mouse homolog displays many features of the human disorder. The group of Dr. Geschwind performed an in vivo screen for drugs that improve the abnormal social behavior of Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. Mutant mice were found to have a decreased number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. Moreover, they showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. In summary, this study indicates a dysregulation of oxytocin system in Cntnap2 knockout mice that can be treated pharmacologically.
Posted by Nicola Brunetti-Pierri