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

  • J Cannabis Res. 2021 Jul 12;3(1):31. doi: 10.1186/s42238-021-00081-1.
Eric Murillo-Rodríguez  1  2 ,  Diana Millán-Aldaco  3 ,  Gloria Arankowsky-Sandoval  4 ,  Tetsuya Yamamoto  5  6 ,  Roger G Pertwee  7 ,  Linda Parker  8 ,  Raphael Mechoulam  9
Affiliations
  • 1. Laboratorio de Neurociencias Moleculares e Integrativas Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab Mérida, Km. 15.5 Carretera Mérida-Progreso, Int. Km. 2 Carretera a Chablekal, Yucatán, C.P. 97,308, Mérida, México. [email protected].
  • 2. Intercontinental Neuroscience Research Group, Mérida, Yucatán, México. [email protected].
  • 3. Depto. de Neurociencia Cognitiva. División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, México.
  • 4. Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, Mérida, Yucatán, México.
  • 5. Intercontinental Neuroscience Research Group, Mérida, Yucatán, México.
  • 6. Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Tokushima, Japan.
  • 7. School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
  • 8. Department of Psychology and Neuroscience Graduate Program, University of Guelph, Guelph, Ontario, Canada.
  • 9. Institute for Drug Research, Medical Faculty, Hebrew University, Jerusalem, Israel.
PMID: 34253253 DOI: 10.1186/s42238-021-00081-1
Abstract

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.

Keywords
Cannabis; Hypothalamus; Rat; Sleep; Wakefulness.
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