Cognitive Enhancer effects of chronic administration of fluoxetine are mediated by 5-HT2aR in mice

SACSON AGOSTINA; MORICI FACUNDO; GALLO FRANCISCO; BEKINSCHTEIN, PEDRO; WEISSTAUB, NOELIA

Mar del Plata

Congreso; XXXII Reunion Anual de la Sociedad Argentina de Investigaciones en Neurociencias; 2017

SAN

n recent years, a body of studies have shown that some serotoninergic drugs have a role as cognitive enhancers. It has been proposed that, like in the case of LSD, this effect could be mediated by the serotonin type 2a receptor (5-HT2aR),. However, little is known about the possible cognitive enhancer effect of other serotoninergic drugs used in medical practice. Fluoxetine (FLX) is a selective serotonin reuptake inhibitor, well known for its antidepressant effects and for being widely prescribed in the treatment of different psychiatric disorders. We intended to analyze if chronic administration of FLX presented cognitive enhancer effects and the role of 5-HT2aR in this effect. For this purpose, we administrated a chronic oral dose of fluoxetine (10mg/kg) to Wild Type (WT) and 5-HT2aR knockout. mice (KO). After 4 weeks of FLX administration, we performed a novel object recognition task. The results showed that a 3 min training session is not enough to generate a long term NOR memory (24 h delayed) independently of the genotype. Interestingly, FLX treatment allowed WT mice to solve the NOR test. However, we didn´t see this effect in KO mice. This result suggests that fluoxetine might have a role as a memory enhancer and that requires 5HT2A signaling