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Updated: Sep 15, 2025
08:49
Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
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LSD's rapid antidepressant effects are modulated by 5-HT2B receptors.
Amel Bouloufa1, Sarah Delcourte1, Renaud Rovera1
1Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, Bron 69500, France.
Summary
Lysergic acid diethylamide (LSD) rapidly reduces depression and anxiety in rats by activating 5-HT2B receptors. This effect was not observed in mice, suggesting species-specific mechanisms for LSD
Area of Science:
- Neuroscience
- Psychopharmacology
- Medicinal Chemistry
Background:
- Serotonergic psychedelics, like lysergic acid diethylamide (LSD), show promise for treating affective disorders.
- LSD interacts significantly with 5-HT2B receptors, which are implicated in regulating anxiety and depression.
Purpose of the Study:
- To investigate the acute effects of LSD on behavior and neuronal activity in rats and mice.
- To determine the role of 5-HT2B receptors in mediating LSD's antidepressant, anxiolytic, and hallucinogenic-like effects.
Main Methods:
- Behavioral tests (forced swim test, open field test, black & white box test) and in vivo electrophysiology were used in naive rats and mice.
- Selective 5-HT2B receptor blockade with RS-127445 and 5-HT depletion were employed to assess mechanisms of action.
Main Results:
- Acute LSD administration produced rapid antidepressant-, anxiolytic-, and hallucinogenic-like effects in rats, accompanied by suppressed 5-HT neuronal activity.
- These effects in rats were blocked by 5-HT2B receptor antagonism and prevented by 5-HT depletion.
- In contrast, LSD did not elicit antidepressant or anxiolytic effects in mice, and its hallucinogenic-like effect was unaffected by 5-HT2B receptor blockade.
Conclusions:
- Acute LSD administration acts as a rapid-onset antidepressant in rats, mediated by 5-HT2B receptor activation.
- The antidepressant and anxiolytic effects of LSD appear to be species-specific, with rats exhibiting these responses while mice do not.
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