OPEN Foundation

Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling

Share This Post

Share on facebook
Share on linkedin
Share on twitter
Share on email

Abstract

A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.13 mg/kg/d, 11 d). In line with former findings, we observe that bulbectomised rats show marked deficits in active avoidance learning. These deficits, similarly as we earlier noted with imipramine, are largely reversed by repeated LSD administration. Additionally, bulbectomised rats exhibit distinct anomalies of monoamine receptor signalling in hippocampus and/or frontal cortex; from these, only the hippocampal decrease in 5-HT2 related [35S]-GTP-gamma-S binding is normalised by LSD. Importantly, the sham-operated rats do not profit from LSD, and exhibit reduced hippocampal 5-HT2 signalling. As behavioural deficits after bulbectomy respond to agents classified as antidepressants only, we conclude that the effect of LSD in this model can be considered antidepressant-like, and discuss it in terms of a re-balance of hippocampal 5-HT2/5-HT1A signalling.

Buchborn, T., Schröder, H., Höllt, V., & Grecksch, G. (2014). Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling. Journal of Psychopharmacology, 28(6), 545-552. https://dx.doi.org/10.1177/0269881114531666
Link to full text

OPEN Foundation

Join ICPR 2022 Online!

ICPR features world-leading experts from many academic disciplines, including psychiatry, psychology, neuroscience, anthropology, ethnobotany, and philosophy who come together to give a scientific conference for academics, therapists, researchers, clinicians, policymakers, and members of the public. Get your ICPR 2022 livestream ticket today and use the code OPENLIVE30 at checkout for a €30 discount.

Learn More

INTERESTED IN PSYCHEDELIC RESEARCH AND THERAPIES?

Subscribe to our new OPEN-Minded newsletter to stay in the loop, hear about our events, and become a part of a community dedicated to advancing psychedelics.

By clicking subscribe, I confirm to receive emails from the OPEN Foundation and agree with its privacy policy.

2 April - New Insights on Addiction & Psychedelic Healing Followed by a Live Q&A!

X