Vardenafil Long-Term Administration Improves Episodic Memory in Aging Female Mice

Age-dependent cognitive decline is associated with a downregulation of the cyclic nucleotide cascade. Through their regulation of the cGMP pathway, phosphodiesterase 5 inhibitors have been proven to enhance episodic memory in rodents and mice and have been proposed as drugs with the potential to counteract aging-dependent cognitive and neurodegenerative disorders. One caveat of this line of research is that these studies have been carried out in male rodents, leaving unknown their effects on female cognition. With the present study, we aim to fill this methodological gap. Twenty-four-month-old female mice were exposed to a continuous 33-day treatment with 2 mg/kg of Vardenafil and tested in the object recognition test, the elevated plus maze, and the open field test. The results show that, compared to females from the control group, Vardenafil-exposed females showed higher discrimination between familiar and novel objects compared to controls both at 1 h and 24 h delays, indicating that Vardenafil enhances episodic memory. No effects of Vardenafil on anxiety-like behaviors were found.