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Anxiety treatment

Does cannabigerol calm rats via serotonin receptors?

Mendiguren A, Aostri E, Rodilla I, et al. · Frontiers in pharmacology · 2023

Open access · cc by · source: Europe PMC

In 176 male rats, cannabigerol weakened α2 and 5-HT1A agonist suppression of LC/DRN firing in slices and reduced anxiety-like behavior in plus-maze and novelty feeding—effects blocked by WAY100635.

Study at a glance

Design
Animal / in-vitro — Male Sprague-Dawley rat LC/DRN slice electrophysiology plus elevated plus maze and novelty-suppressed feeding, with WAY100635 challenge
N
N=176 · 176 rats total: 118 behavioral, 58 electrophysiology
Population
Male Sprague-Dawley rats (200–300 g); locus coeruleus and dorsal raphe nucleus slices plus in vivo anxiety tests
Outcome
NA and 5-HT neuron firing modulation by α2 and 5-HT1A agonists, plus anxiolytic-like EPMT/NSFT behavior

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Key findings

CBG barely changed baseline firing and did not block NA or 5-HT itself, but reduced inhibition by UK14304 and ipsapirone. WAY100635 restored firing after ipsapirone; CBG did not. In vivo, CBG increased open-arm time and cut feeding latency, prevented by WAY100635.

Methodology

Recorded locus coeruleus NA and dorsal raphe 5-HT cell firing in slices with CBG (30 μM) versus NA, UK14304, 5-HT, ipsapirone, and WAY100635, and tested CBG 10 mg/kg i.p. in elevated plus maze and novelty-suppressed feeding with a 5-HT1A antagonist pretreatment.

Limitations

Rat slice and maze tests do not establish human anxiolysis or a direct receptor binding mechanism; authors call the slice effect an unknown indirect action.

How this study connects

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