Audiogenic Seizure Assay

AGS experiments were performed as previously described (32). Fmr1-KO and WT mice were housed on static racks to prevent auditory desensitization that occurs with chronic exposure to the ambient noise of ventilated racks. For acute dosing experiments, mice received i.p. injections with vehicle or drug in a separate room 1–2 h prior to exposure to the alarm in a separate room. For chronic CTEP dosing experiments, mice received 3 i.p. CTEP or vehicle injections, one every 48 h, with the final dose occurring 1–2 h prior to testing. All injections began at P23-25 (immediately following weaning). Animals were habituated to the behavioral chamber (28 × 17.5 × 12 cm transparent plastic box) for 1 min prior to stimulus onset. The auditory stimulus was a 125 dB at 0.25 m siren (modified personal alarm, RadioShack model 49-1010, powered from a DC converter). Seizures were scored for incidence during a 2-min stimulus presentation or until the animal reached an AGS endpoint. Wild running/jumping, status epilepticus, respiratory arrest or death were all scored as seizure activity.