The cannabinoid CB2 receptor: improvement of sleep or memory in rotenone model of Parkinson's disease

Abstract

The impact of cannabinoid CB₂ receptor modulation on the non-motor symptoms of Parkinson's disease remains unknown. We investigated the role of nigrostriatal CB₂ receptors modulation in reversing alterations in sleep macrostructure, inter-hemispheric synchronization dynamics, and memory consolidation in the rotenone model of Parkinson's disease. Male Wistar rats (n = 65) underwent stereotaxic surgery for the administration of either rotenone (12 μg/μl) or dimethyl sulfoxide (vehicle, 10 % v/v) into the substantia nigra pars compacta. Seven days later, the rotenone-treated animals received intrastriatal injections of either dimethyl sulfoxide (vehicle, 10 % v/v), GW405833 (partial agonist of CB₂ receptors, 10 μg/μl), or AM630 (antagonist/inverse agonist of CB₂ receptors, 3 μg/μl). One group of animals underwent 6 h of sleep-wake recording, while another group performed object recognition and open field tests. Real-time polymerase chain reaction was conducted to determine striatal transcript levels of CB₁ and CB₂ receptors. Infusion of AM630 reversed the rotenone-induced alterations in sleep macrostructure and inter-hemispheric synchronization dynamics. This modulation led to increased sleep efficiency (p < 0.01), higher probability of shorter desynchronization events (p < 0.01), and reduced transition rate from synchronized to desynchronized states (p < 0.05). Conversely, GW405833, but not AM630, reversed the rotenone-induced impairment in object recognition memory (p < 0.01). No significant effects were observed on striatal cannabinoid receptors transcripts levels. These findings suggest that CB₂ receptors modulation is associated with paradoxical outcomes in terms of non-motor signs of Parkinson's disease, indicating somewhat independent mechanisms underlying sleep and memory alterations in the rotenone model of the disease.