Inhibition of fatty-acid amide hydrolyse (FAAH) exerts cognitive improvements in male but not female rats.

OBJECTIVES:

The endocannabinoid system is implicated in the regulation of various brain functions including cognition, memory, and behavior. It has been shown that inhibition of the endocannabinoid-degrading enzyme fatty acid amid hydrolase (FAAH) enhances the memory and learning in males. Given the fact that sexual dimorphism exists in the different components of the endocannabinoid system, the aim of this study was to test the hypothesis that cognition enhancing effect of the acute inhibition of FAAH by URB597 is gender dependent.

METHODS:

In the study, 32 adult male and female Sprague-Dawley rats were used. They were treated with a single intraperitoneal injection of FAAH inhibitor URB597 (0.3 mg/kg) or vehicle 40 min before behavioral testing. The novel object recognition test was used as a working memory task to assess cognitive performance.

RESULTS:

Neither the treatment nor the gender significantly affected the velocity, the total distance travelled and the time spent exploring the familiar object. The recognition of the object was influenced by both URB597 and gender. Male rats treated with URB597 displayed significantly increased novel object exploration compared to males treated with vehicle as well as to female rats treated with URB597. Single administration of URB597 significantly enhanced the recognition index in male, but not female rats.

CONCLUSIONS:

The results demonstrate that the positive effects of FAAH inhibition on the cognition are gender dependent. It is likely that male rats are more vulnerable to the modulation of the endocannabinoid system than female rats.