Cannabidiol gaat de psychotrope bijwerkingen van {Delta} -9-Tetrahydrocannabinol in de ventrale hippocampus tegen door bidirectionele controle van ERK1-2 fosforylering


Translating…


De Beste Kwaliteit CBD Olie?

MHBioShop CBD Olie Specialist  


Pour la meilleure qualité d’Huile de CBD Visitez

HuileCBD.be specialiste Huile de CBD


   

Research Articles, Behavioral/Cognitive

Roger Hudson, Justine Renard, Christopher Norris, Walter J. Rushlow and Steven R. Laviolette

Journal of Neuroscience 30 October 2019, 39 (44) 8762-8777; DOI: https://doi.org/10.1523/JNEUROSCI.0708-19.2019

Loading

Abstract

Evidence suggests that the phytocannabinoids Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) differentially regulate salience attribution and psychiatric risk. The ventral hippocampus (vHipp) relays emotional salience via control of dopamine (DA) neuronal activity states, which are dysregulated in psychosis and schizophrenia. Using in vivo electrophysiology in male Sprague Dawley rats, we demonstrate that intra-vHipp THC strongly increases ventral tegmental area (VTA) DA neuronal frequency and bursting rates, decreases GABA frequency, and amplifies VTA beta, gamma and ε oscillatory magnitudes via modulation of local extracellular signal-regulated kinase phosphorylation (pERK1–2). Remarkably, whereas intra-vHipp THC also potentiates salience attribution in morphine place-preference and fear conditioning assays, CBD coadministration reverses these changes by downregulating pERK1–2 signaling, as pharmacological reactivation of pERK1–2 blocked the inhibitory properties of CBD. These results identify vHipp pERK1–2 signaling as a critical neural nexus point mediating THC-induced affective disturbances and suggest a potential mechanism by which CBD may counteract the psychotomimetic and psychotropic side effects of THC.

SIGNIFICANCE STATEMENT Strains of marijuana with high levels of delta-9-tetrahydrocannabinol (THC) and low levels of cannabidiol (CBD) have been shown to underlie neuropsychiatric risks associated with high-potency cannabis use. However, the mechanisms by which CBD mitigates the side effects of THC have not been identified. We demonstrate that THC induces cognitive and affective abnormalities resembling neuropsychiatric symptoms directly in the hippocampus, while dysregulating dopamine activity states and amplifying oscillatory frequencies in the ventral tegmental area via modulation of the extracellular signal-regulated kinase (ERK) signaling pathway. In contrast, CBD coadministration blocked THC-induced ERK phosphorylation, and prevented THC-induced behavioral and neural abnormalities. These findings identify a novel molecular mechanism that may account for how CBD functionally mitigates the neuropsychiatric side effects of THC.

View Full Text

Log in through your institution

If your organization uses OpenAthens, you can log in using your OpenAthens username and password.

To check if your institution is supported, please see this list.

Contact your library for more details.

Pay Per Article – You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access – You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

Lees Meer

Leave a Comment