Chronic modulation of endocannabinoid receptors does not impact hyperactivity, risk behavior, and working memory in...

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by impairments in executive functions, including behavioral inhibition and working memory. The most widely accepted neurobiological explanation for ADHD is related to dopaminergic hypofunction. The dopaminergic system is modulated by endocannabinoid ligands, primarily through the action of cannabinoid receptors type 1 and 2 (CB1R and CB2R) within frontostriatal circuits. Spontaneously hypertensive rats (SHR) are a widely used animal model for studying the neurobiology of ADHD. Our recent study demonstrated that acute treatment with synthetic CB1R and CB2R ligands increased hyperactivity and risk-taking behavior in SHR. We now investigate how chronic modulation of these receptors affects hyperactivity, risk-taking behavior, and working memory assessment in SHR. As expected, the SHR exhibited hyperactivity, difficulties in risk assessment, impaired working memory, and increased risk-taking behavior. Notably, females SHR displayed higher levels of locomotion and risk-taking behavior than their male counterparts, regardless of treatment. Chronic modulation of CB1R and CB2R did not lead to significant changes in any of the evaluated behavioral parameters. Further research is needed to understand both the acute and chronic effects of manipulating cannabinoid receptors and endocannabinoids in the context of ADHD.