Autism spectrum disorder (ASD) is characterized by the expression of restricted repetitive behaviors (RRBs) and impairments in social recognition and communication. Previous studies have found that specific serotonin (5-HT) receptor modulation can attenuate repetitive behaviors expressed in specific mouse strains. The present study examined how 5-HT6 receptor blockade impacts the expression of repetitive behaviors in two different mouse strains that demonstrate elevated restricted, repetitive behavior and impairments in social behavior. BTBR T+ Itpr3tf /J (BTBR), C58/J (C58) and control C57BL/6J strains were behaviorally tested after acute treatment with the 5-HT6 receptor antagonist BGC 20-761 (BGC) or vehicle. BTBR mice express high levels of self-grooming behavior while C58 mice display high rates of repetitive jumping behavior. Similarly, the effect of 5-HT6 receptor blockade was also tested on social approach behaviors in both strains. BGC significantly reduced repetitive grooming in both female and male BTBR mice compared to vehicle-treated BTBR mice. BGC treatment did not attenuate social approach impairments in either female or male BTBR mice compared to vehicle-treated BTBR mice. Follow-up dose response studies were conducted on repetitive grooming and locomotor activity in BTBR mice. All doses reduced repetitive grooming in female and male BTBR mice. Acute treatment with BGC only reduced locomotor activity with the lower doses. In C58 mice, BGC treatment did not significantly attenuate flipping or general social approach behaviors. Instead, BGC significantly increased social sniff time in female C58 mice. While 5-HT6 receptor blockade did not attenuate the social impairments found in BTBR mice, this treatment did increase sniff time in female C58 mice. Although the lower doses of BGC deduced locomotion, the higher dose attenuated repetitive grooming in BTBR mice while sparing locomotor activity. Together these findings suggest the therapeutic effects of 5-HT6 receptor blockade are complex and may be specific to the types of repetitive behaviors expressed.

自闭症谱系障碍（ASD）的特征是受限的重复性行为（RRB）的表达以及社会认知和沟通障碍。先前的研究发现，特定的5-羟色胺（5-HT）受体调节可以减弱特定小鼠品系中表达的重复行为。本研究研究了5-HT6受体阻滞如何影响两种不同小鼠品系中重复性行为的表达，这些品系显示出受限的重复性行为和社交行为受损。在使用5-HT6受体拮抗剂BGC 20-761（BGC）或溶媒进行急性治疗后，对BTBR T + Itpr3tf / J（BTBR），C58 / J（C58）和对照C57BL / 6J菌株进行了行为测试。BTBR小鼠表现出高水平的自我修饰行为，而C58小鼠表现出高水平的重复跳跃行为。同样，还测试了两种菌株中5-HT 6受体阻断的作用对社交方式行为的影响。与媒介物处理的BTBR小鼠相比，BGC显着减少了雌性和雄性BTBR小鼠的重复修饰。与媒介物处理的BTBR小鼠相比，BGC治疗并未减轻雌性或雄性BTBR小鼠的社交方式障碍。对BTBR小鼠的重复修饰和运动活性进行了后续剂量反应研究。所有剂量都减少了雌性和雄性BTBR小鼠的重复修饰。BGC的急性治疗只能以较低的剂量降低运动能力。在C58小鼠中，BGC治疗并未显着减弱翻转或一般社交方式的行为。相反，BGC显着增加了雌性C58小鼠的社交嗅觉时间。尽管5-HT6受体阻滞并不能减轻BTBR小鼠的社交障碍，但这种治疗确实增加了雌性C58小鼠的嗅觉时间。尽管较低剂量的BGC会降低运动能力，但较高剂量的BTBR小鼠会减弱重复修饰作用，同时保留运动能力。这些发现共同表明5-HT6受体阻滞的治疗作用是复杂的，并且可能对所表达的重复行为类型具有特异性。