The 5-HT1A receptor and the stimulus effects of LSD in the rat.
Chad J Reissig, Justin R Eckler, R A Rabin, Jerrold C Winter
Psychopharmacology October 2005 DOI: 10.1007/s00213-005-0068-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study (drug discrimination) Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Male Fischer 344 rats |
| Interventions | LSD 8-OH-DPAT buspirone gepirone ipsapirone WAY-100 635 |
| Dose | LSD 0.1 mg/kg i.p.; WAY-100,635 0.3 mg/kg s.c. |
| Topics | LSD Serotonin |
| Key findings | 5-HT1A receptor agonists increased LSD-induced stimulus control, and this potentiation was abolished by the 5-HT1A antagonist WAY-100,635, supporting a modulatory role for the 5-HT1A receptor in LSD's discriminative stimulus effects. |
Abstract
It has been suggested that the 5-HT1A receptor plays a significant modulatory role in the stimulus effects of the indoleamine hallucinogen lysergic acid diethylamide (LSD). The present study sought to characterize the effects of several compounds with known affinity for the 5-HT1A receptor on the discriminative stimulus effects of LSD. Twelve male Fischer 344 rats were trained in a two-lever, fixed-ratio (FR) 10, and food-reinforced task with LSD (0.1 mg/kg, i.p.; 15-min pretreatment) as a discriminative stimulus. Combination and substitution tests with the 5-HT(1A) agonists, 8-OH-DPAT, buspirone, gepirone, and ipsapirone, with LSD-induced stimulus control were then performed. The effects of these 5-HT1A ligands were also tested in the presence of the selective 5-HT1A receptor antagonist, WAY-100,635 (0.3 mg/kg, s.c.; 30-min pretreatment). In combination tests, stimulus control by LSD was increased by all 5-HT1A receptor ligands with agonist properties. Similarly, in tests of antagonism, the increase in drug-appropriate responding caused by stimulation of the 5-HT1A receptor was abolished by administration of WAY-100,635. These data, obtained using a drug discrimination model of the hallucinogenic effects of LSD, provide support for the hypothesis that the 5-HT1A receptor has a significant modulatory role in the stimulus effects of LSD.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 47
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacology, Biochemistry, and Behavior 2006
- Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis. Psychiatry Research May 1, 2024
- d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology International Journal of Molecular Sciences November 23, 2016
and 42 more in the library
Cites 17
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Science August 16, 1968
- Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacology, Biochemistry, and Behavior August 1, 1990
- The effects of 8-hydroxy-2-(di-n-propylamino)tetralin and other serotonergic agonists on performance in a radial maze: a possible role for 5-HT1A receptors in memory. Pharmacology, Biochemistry, and Behavior August 1, 1987
- Neuropharmacological reassessment of the discriminative stimulus properties ofd-lysergic acid diethylamide (LSD) Psychopharmacology 1987
and 12 more in the library