The novel cannabinoid agonist AM 411 produces a biphasic effect on accuracy in a visual target detection task in rats

Cannabinoid agonists have been shown to produce dose-related impairments in several measures of cognitive performance. However, it is unclear if low doses of cannabinoid CB1 agonists, or CB1 antagonists, can facilitate aspects of stimulus detection. The present study employed an operant procedure involving visual stimulus detection in rats. The task was found to be sensitive to the muscarinic acetylcholine antagonist scopolamine. The CB1 antagonist AM 251 did not affect stimulus detection processes across a broad range of doses. However, the novel CB1 agonist AM 411 produced a biphasic effect, with the two lowest doses (0.25 and 0.5 mg/kg) enhancing accuracy. AM 411 changed patterns of responding toward runs of consecutive errors on only one of the two levers. It produced a biphasic effect on consecutive errors on the lever associated with a higher level of errors, with decreases in errors following the lower doses (0.25 and 0.5 mg/kg) and increases following the highest dose (2.0 mg/kg). These effects were not accompanied by changes in measures of bias commonly used to uncover such patterns in rodent operant models of cognitive performance. In contrast to the cognitive impairment seen after administration of moderate to high doses of CB1 agonists, it appears that low doses of some CB1 agonists may be capable of enhancing stimulus detection processes.