CB1 receptor antagonist AM251 differentially affects attention and impulsivity in rats

Abstract

Recent studies suggest that the cannabinoid system may mediate attention and impulsive behavior (Arguello & Jentsch, 2004; Pattij et al., 2007). CB1 receptor antagonist SR141416A (SR) was found to dose dependently reduce the number of premature responses and slightly improved attentional performance in rats trained to perform the five-choice serial reaction time task (5-CSRTT), a measure of attention and impulsivity designed for animals. However, SR did not reduce other varieties of impulsive behavior in other tasks (Pattij et al., 2007). The aim of the current investigation was to further explore the role of CB1 receptor antagonism on attention and impulsive behavior by administering the more selective antagonist AM251 to rats trained to perform the 5-CSRTT. Furthermore, to create an attentional and behavioral challenge, rats were exposed to task variations designed to increase attentional demands and ability to inhibit impulsive behaviors.

Eight male Long-Evans rats were trained to perform the 5-CSRTT. Upon reaching a criterion level of performance in the 5-CSRTT. rats were administered (i.p.) CB1 receptor antagonist AM251 (2 and 4 mg/kg) and vehicle in the standard 5-CSRTT task and two variations: variable long inter-trial interval and variable stimulus duration conditions. The 2mg dose significantly reduced premature responding and increased attention capability while 4mg had little effect on performance in the standard task. The effects of AM251 on premature responding were dependent on the level of inter-trial interval. Both doses of AM251 had little effect on performance in the variable stimulus duration task. This investigation further supports CB1 receptor involvement in attention and impulsive behavior.