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Background  Cannabidiol (CBD), the non-psychotropic compound from  Cannabis sativa,  shows positive results on controlling several health disturbances; however, comparable data regarding additional chemical from  C. sativa,  such as cannabidiolic acid (CBDA), is scarce due to its instability. To address this limitation, a stable CBDA analogue, CBDA methyl ester (HU-580), was synthetized and showed CBDA-like effects. Recently, we described that HU-580 increased wakefulness and wake-related neurochemicals.    Objective  To extend the comprehension of HU-580´s properties on waking, the  c -Fos and NeuN expression in a wake-linked brain area, the hypothalamus was evaluated.    Methods   c -Fos and NeuN expression in hypothalamic sections were analyzed after the injections of HU-580 (0.1 or 100 μg/kg, i.p.).    Results  Systemic administrations of HU-580 increased  c -Fos and neuronal nuclei (NeuN) expression in hypothalamic nuclei, including the dorsomedial hypothalamic nucleus dorsal part, dorsomedial hypothalamic nucleus compact part, and dorsomedial hypothalamic nucleus ventral part.    Conclusion  HU-580 increased  c -Fos and NeuN immunoreactivity in hypothalamus nuclei suggesting that this drug might modulate the sleep–wake cycle by engaging the hypothalamus.

journal of cannabis research

Assessing the treatment of cannabidiolic acid methyl ester: a stable synthetic analogue of cannabidiolic acid on c-Fos and NeuN expression in the hypothalamus of rats