Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al.
Anthony G Romano, Jennifer L Quinn, Luchuan Li, Kuldip D. Dave, Emmanuelle A. D. Schindler, Vincent J. Aloyo, John A. Harvey
Psychopharmacology October 1, 2010 DOI: 10.1007/s00213-010-2004-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rabbits |
| Interventions | LSD DOI |
| Dose | 3 or 10 nmol per side |
| Duration | Eight conditioning sessions with one-day post-infusion DOI test |
| Topics | LSD Serotonin |
| Keywords | Learning enhancement Accelerated learning Learning improvement Enhanced learning Conditioning Conditioned responses Serotonin receptors Receptor desensitization Hippocampus Brain's learning hub Brain region |
| Citations | 42 |
| Key findings | LSD enhances Pavlovian conditioning by desensitizing 5-HT(2A) receptors in the dorsal hippocampus. |
Abstract
Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT(2A)-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning. This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT(2A)-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning. LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT(2A) receptor as measured by a decrease in DOI-elicited head bobs. Acute parenteral or intrahippocampal LSD elicited a 5-HT(2A) but not a 5-HT(2C)-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls. LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT(2A) receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT(2A) receptor within the hippocampus as a result of repeated administration of its agonist (LSD).
Comparable studies
Other experimental studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neural correlates of the LSD experience revealed by multimodal neuroimaging. Human participants | 2016 | Experimental study | |
| Crystal structure of an LSD-bound human serotonin receptor | 2017 | Experimental study with structural biology and molecular dynamics simulations | |
| Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Midbrain neurons containing serotonin | 1968 | Experimental study | |
| Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain | 2017 | Experimental study | |
| LSD-Assisted Psychotherapy in Patients with Terminal Cancer Cancer patients | 1973 | Experimental study | n = 60 |
Citations in the library
Cited by 31
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- LSD-induced entropic brain activity predicts subsequent personality change. Human Brain Mapping May 6, 2016
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- The paradoxical psychological effects of lysergic acid diethylamide (LSD) Psychological Medicine February 5, 2016
- Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting Psychopharmacology October 24, 2018
and 26 more in the library
Cites 8
- 2,5-Dimethoxy-4-methyl-amphetamine (STP): A New Hallucinogenic Drug Science November 3, 1967
- Lysergic Acid Diethylamide (LSD-25): I. Physiological and Perceptual Responses The Journal of Psychology 1955
- Pharmacology of Lysergic Acid Diethylamide and Some of Its Related CompoundS Journal of Pharmacy and Pharmacology September 1, 1957
- Hallucinogens. Pharmacology & Therapeutics February 1, 2004
- Effect of serotonin depletion on 5-HT2A-mediated learning in the rabbit: evidence for constitutive activity of the 5-HT2A receptor in vivo. Psychopharmacology January 2006
and 3 more in the library