AMPAR modulator-12

Wistar Kyoto (WKY) rats (male, 5-11 weeks old, congenital depressive phenotype model)^[1]

1 mg/kg

i.v.; single administration; daily for 7 days

Significantly reduced immobility time in the FST, shortened latency to touch and feed in the NSFT, and increased sucrose preference in the SPT at 3 h post-treatment compared to vehicle.
Showed significantly reduced immobility time in the FST on day 8 and day 15 post-withdrawal after 7 days of daily administration; this effect was abolished by co-administration of the AMPAR antagonist GYKI53655.
Significantly increased sucrose preference in the SPT on day 8 and day 15 post-withdrawal, and reduced immobility time in the FST on day 22 post-withdrawal.
Showed no significant differences in locomotor activity compared to vehicle-treated rats.
Significantly restored mEPSC amplitude and increased mEPSC frequency in layer 2/3 pyramidal neurons of the mPFC 30 min post-injection compared to vehicle.
Showed significantly increased mEPSC and mIPSC amplitudes in mPFC pyramidal neurons, and significantly reduced burst firing in lateral habenula (LHb) neurons seven days post-withdrawal from daily administration compared to vehicle controls.
Downregulated Nox1 expression by 2.61-fold compared to ketamine treatment, and by 2.28-fold compared to intact rats in bulk RNA sequencing of mPFC tissue 7 days post-withdrawal.