Atomoxetine Decreases Vulnerability to Develop Compulsivity in High Impulsive Rats

作者：Ansquer Solene; Belin Rauscent Aude; Dugast Emilie; Duran Theo; Benatru Isabelle; Mar Adam C; Houeto Jean Luc; Belin David^*

来源：Biological Psychiatry, 2014, 75(10): 825-832.

DOI：10.1016/j.biopsych.2013.09.031

• Atomoxetine
• compulsivity
• five-choice serial reaction time task
• impulsivity trait
• obsessive-compulsive spectrum disorders
• schedule-induced polydipsia
• Tourette%26apos
• s syndrome

Background: The factors contributing to the development and severity of obsessive-compulsive spectrum disorders such as obsessive-compulsive disorder, Tourette%26apos;s syndrome, pathological gambling, and addictions remain poorly understood, limiting the development of therapeutic and preventive strategies. Recent evidence indicates that impulse-control deficits may contribute to the severity of compulsivity in several of these disorders. This suggests that impulsivity may be a transnosological endophenotype of vulnerability to compulsivity. However, the precise nature of the link between impulsivity and compulsivity in anxiety-related compulsive disorders remains unknown. %26lt;br%26gt;Methods: We investigated the relationship between impulsivity and the development of a compulsive behavior in rats, which captures the hallmarks of compulsivity as defined in the DSM-IV-namely, that it is maladaptive, excessive, repetitive, and anxiolytic. %26lt;br%26gt;Results: We demonstrate that a high-impulsivity trait, as measured in the five-choice serial reaction time task, predicts an increased propensity to develop compulsivity as measured in a schedule-induced polydipsia procedure. Trait impulsivity and compulsivity were nonlinearly related. This impulsivity-compulsivity relationship was lost after the development of compulsivity or under chronic treatment with atomoxetine, a noradrenergic reuptake inhibitor used to treat attention-deficit/ hyperactivity disorder. Atomoxetine treatment both decreased impulsivity and prevented the development of compulsivity in high-impulsive animals. %26lt;br%26gt;Conclusions: These observations provide insight into the reciprocal influence of impulsivity and compulsivity in compulsive disorders and suggest that atomoxetine may be a useful treatment for patients suffering from obsessive-compulsive spectrum disorders with high impulsivity.

• 出版日期2014-5-15