Effect of 5-HT6 Modulation on Behavioral Flexibility and Working Memory in Mice

Event Center BC

Repetitive behaviors are a prevailing symptom across several neuropsychiatric and neurodevelopmental disorders, including autism spectrum disorder (ASD). Repetitive behaviors with restricted interests (RRBs) are a core feature of ASD and currently there is lack of effective treatments for attenuation of these behaviors. In the search of new therapeutic targets, the 5-hydroxytrptamine 6 (5-HT6) receptor is of interest because blockade has shown to have pro-cognitive affects and shows promise in attenuation of behavioral inflexibility. The current experiments aim to better understand how increased 5-HT6 receptor activation may lead to learning impairments in C57BL/6J mice. Mice were tested on three separate behavioral measures including locomotor activity, spontaneous alternation (working memory) and probabilistic reversal learning (behavioral flexibility). Mice received an acute injection of vehicle solution or 2mg/kg EMD386088. We predicted that the 5-HT6 receptor agonist would impair both spontaneous alternation and probabilistic reversal learning performance. Vehicle and EMD386088 treated mice displayed comparable locomotor activity. EMD386088 impaired spontaneous alternation performance but facilitated performance on the probabilistic reversal learning task. Because these tasks measure working memory and behavioral flexibility and different areas Repetitive behaviors are a prevailing symptom across several neuropsychiatric and neurodevelopmental disorders, including autism spectrum disorder (ASD). Repetitive behaviors with restricted interests (RRBs) are a core feature of ASD and currently there is lack of effective treatments for attenuation of these behaviors. In the search of new therapeutic targets, the 5-hydroxytrptamine 6 (5-HT6) receptor is of interest because blockade has shown to have pro-cognitive affects and shows promise in attenuation of behavioral inflexibility. The current experiments aim to better understand how increased 5-HT6 receptor activation may lead to learning impairments in C57BL/6J mice. Mice were tested on three separate behavioral measures including locomotor activity, spontaneous alternation (working memory) and probabilistic reversal learning (behavioral flexibility). Mice received an acute injection of vehicle solution or 2mg/kg EMD386088. We predicted that the 5-HT6 receptor agonist would impair both spontaneous alternation and probabilistic reversal learning performance. Vehicle and EMD386088 treated mice displayed comparable locomotor activity. EMD386088 impaired spontaneous alternation performance but facilitated performance on the probabilistic reversal learning task. Because these tasks measure working memory and behavioral flexibility and different areas