Cognition, Behavior, and Memory
Author: Fabrizio Stanglino | Email: fstanglino@mi.unc.edu.ar
Fabrizio Stanglino1°2°, Roberto Sebastian Miranda Morales1°2°, María Gabriela Paglini1°3°, Florencia Dadam1°2°
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
Actually, 2 billion people globally consume or abuse alcohol, causing 3.2% of deaths. Attention-Deficit/Hyperactivity Disorder (ADHD), the most common behavioral disorder in childhood, affects around 4% of children and impacts their social and academic functioning. The psychostimulant methylphenidate (MTPH) is the most commonly treatment for ADHD. Given MTPH’s amphetamine-like pharmacodynamics and the influence of early substance use on addiction risk, chronic MTPH use during childhood or adolescence may increase the likelihood of substance abuse in adulthood. We studied the effects of chronic MTPH treatment during childhood/adolescence on ethanol motor-stimulating effects in adulthood in an ADHD animal model. We used p35KO transgenic mice and wild-type (WT) controls, both chronically treated with MTPH from postnatal days 21-31 and tested for ethanol-induced stimulation and sensitization in adulthood. We found that p35KO-CON and MTPH treated mice exhibited ethanol-induced stimulation only after 14 days of repeated exposure, without developing sensitization, unlike the WT controls. However, only p35KO-MTPH-treated mice exhibited a sustained stimulant effect.
In conclusion, our study underscores the critical role of the Cdk5/p35 complex in ethanol stimulant response. Also, we demonstrate that chronic psychostimulant treatment during preadolescence leads to a loss of the sensitization phenomenon, suggesting that prolonged MTPH treatment may pose a potential risk of addiction.