5-HT1B/1A Receptor Agonist RU24969 Impairs Reversal Learning in C57BL/6 Mice

SMSU Event Center BC

Obsessive-compulsive disorder (OCD) is defined as insistent urges, persistent thoughts, and/or repetitive behaviors that are difficult to inhibit. Pharmacological alterations to the serotonergic system have shown to induce OCD-like behaviors in mouse models. Moreover, the serotonin-1B/1A receptor (5-HT1B/1A) agonist RU24969 has been shown to induce OCD-like behavior in rodents and induce deficits in working memory as evidenced by impaired performance on the delayed alternation task. However, there seems to be a lack of understanding of how RU24969 impacts learning and memory. OCD’s symptomology includes excessive habit formation that can impact goal-directed learning and cognitive flexibility. Therefore, if RU24969 is pharmacologically inducing OCD, then it is important to investigate its impact on learning, memory, and executive function. The current study examines the effects of systemic 5-HT1B/1A receptor agonist RU24969 (0.1 or 1.0 mg/kg) treatment on cognitive flexibility using the spatial probabilistic reversal learning maze task in C57BL/6 mice. Testing included acquisition of spatial discrimination and subsequent reversal learning. Before acquisition, all mice were treated with a vehicle treatment. Measures of behavioral flexibility were tested in a spatially dependent T-maze using an 80:20 probabilistic reinforcement schedule until a criterion of six correct choices was made. Before the reversal phase, mice were injected with either RU24969 or vehicle and the reinforcement contingencies were reversed to examine how many trials were required for mice to reach learning criterion. Findings indicate that acute RU24969 treatment significantly impaired reversal learning performance.