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Does cannabigerol calm rats via serotonin receptors?

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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.

Source

Cannabigerol modulates α<sub>2</sub>-adrenoceptor and 5-HT<sub>1A</sub> receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat

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

doi.org/10.3389/fphar.2023.1183019Read the full paper ↗21 citationscc by

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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Does cannabigerol calm rats via serotonin receptors?

These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.

176 male Sprague-Dawley rats were used (118 behavioral; 58 electrophysiology).

Male Sprague-Dawley (200–300 g) rats (total, n = 176; behavioral tests, n = 118; and electrophysiological assays, n = 58)

CBG was tested at 30 μM for 10 min in slices.

CBG (30 μM, 10 min) slightly changed the firing rate of NA cells but failed to alter the inhibitory effect of NA (1–100 µM)
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What they did

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.

What they found

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.

The limits

What it doesn't show

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.

Key terms

Cannabigerol (CBG)
Non-psychoactive phytocannabinoid tested at 30 μM in slices and 10 mg/kg i.p. in vivo.
Locus coeruleus
Main noradrenergic nucleus; firing regulated by α2-adrenoceptors.
Dorsal raphe nucleus
Principal 5-HT nucleus; 5-HT1A autoreceptors inhibit 5-HT cell firing.
UK14304
Selective α2-adrenoceptor agonist whose inhibitory effect shrank in the presence of CBG.
Ipsapirone
5-HT1A agonist; CBG reduced its firing inhibition but did not reverse it.
WAY100635
5-HT1A antagonist that restored DRN firing and blocked CBG’s NSFT effect.

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Common questions

How many rats?

176 (118 behavior; 58 electrophysiology).

Did CBG block NA itself?

No—it failed to alter NA (1–100 µM) inhibition.

What in vivo tests?

Elevated plus maze and novelty-suppressed feeding.

Was 5-HT1A required for anxiolysis?

WAY100635 prevented CBG’s reduced latency to feed.

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