S-047 | The influence of the Cdk5/p35 complex on working memory and the effects of acute treatment with methylphenidate and fluoxetine in a mouse model of Attention Deficit Hyperactivity Disorder.

Cognition, Behavior, and Memory
Author: Franco Adrián Haehnel | Email: franco.haehnel@mi.unc.edu.ar

Franco Adrián Haehnel^1°, Florencia Dadam^1°2°, Osvaldo Martín Basmadjian^1°,  María Gabriela Paglini^1°3°

^1° Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-UNC.1 Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-UNC.
^2° Facultad de Psicologia, Universidad Nacional de Córdoba
^3° Instituto de Virología “Dr. José María Vanella”, In.Vi.V.-CONICET-UNC

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by hyperactivity, impulsivity, and working memory (WM) deficits, which impair short-term memory used for the planning and execution of cognitive functions. The treatment of ADHD typically involves the use of psychostimulants such as methylphenidate (MTPH), while fluoxetine (FLX) may be incorporated when there is comorbidity with depressive disorders. We previously demonstrated that p35KO mice, which lack the activating subunit of Cdk5, exhibit key features of ADHD animal models.
We aimed to investigate the contribution of the Cdk5/p35 complex to WM and explore the impact of acute MTPH and FLX treatments, taking into account potential sex differences. We used p35KO mice and wild-type (WT) controls. Between postnatal days 21-25, the animals received acute treatment with MTPH, FLX, MTPH+FLX, or saline solution, followed by a Y-maze test to assess WM. Both, male and female p35KO mice exhibited impaired WM compared with WT mice. However, acute treatment with MTPH or FLX reversed the WM deficit only in male mice, these effects were not seen with combined treatment. Additionally, these treatments reduced WM performance in WT female mice.
In conclusion, our study highlights the crucial role of the Cdk5/p35 complex in WM processes. It also demonstrates that acute treatment with MTPH or FLX can restore WM deficits in p35KO-male mice, although these treatments may pose risks for WT animals.