Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice
Michael A. Benneyworth, Randy L Smith, Robert J. Barrett, Elaine Sanders‐bush
Psychopharmacology January 11, 2005 DOI: 10.1007/s00213-004-2108-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | C57Bl/6J mice |
| Interventions | Lysergic acid diethylamide 2 5-dimethoxy-4-bromoamphetamine 8-hydroxy-2-(di-n-propylamino)-tetralin MDL 100907 WAY 100635 |
| Dose | 0.45 mg/kg LSD, 1.0 mg/kg (-)DOB, 1.6 mg/kg 8-OH-DPAT |
| Topics | LSD |
| Keywords | Pharmacology Hallucinogen Antagonist Stimulus control Partial agonist Self-administration Receptor |
| Citations | 38 |
| Key findings | In mice, the stimulus effects of LSD involve both 5-HT(2A) and 5-HT(1A) receptor components. |
Abstract
RationaleThe drug discrimination procedure is the most frequently used in vivo model of hallucinogen activity. Historically, most drug discrimination studies have been conducted in the rat. With the development of genetically modified mice, a powerful new tool has become available for investigating the mechanisms of drug-induced behavior. The current paper is part of an ongoing effort to determine the utility of the drug discrimination technique for evaluating hallucinogenic drugs in mice.ObjectiveTo establish the training procedures and characterize the stimulus properties of (+)lysergic acid diethylamide (LSD) in mice.MethodsUsing a two-lever drug discrimination procedure, C57Bl/6J mice were trained to discriminate 0.45 mg/kg LSD vs saline on a VI30 sec schedule of reinforcement, with vanilla-flavored Ensure serving as the reinforcer.ResultsAs in rats, acquisition was orderly, but the training dose was nearly five-fold higher for mice than rats. LSD lever selection was dose-dependent. Time-course studies revealed a rapid loss of the LSD stimulus effects. The 5-HT(2A/2C) receptor agonist, 2,5-dimethoxy-4-bromoamphetamine [(-)DOB] (1.0 mg/kg), substituted fully for LSD and the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) (1.6 mg/kg), substituted partially for LSD. Pretreatment with the 5-HT(2A) receptor-selective antagonist, MDL 100907, or the 5-HT(1A)-selective antagonist WAY 100635, showed that each antagonist only partially blocked LSD discrimination. Substitution of 1.0 mg/kg (-)DOB for LSD was fully blocked by pretreatment with MDL 100907 but unaltered by WAY 100635 pretreatment.ConclusionsThese data suggest that in mice the stimulus effects of LSD have both a 5-HT(2A) receptor and a 5-HT(1A) receptor component.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 33
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen Psychopharmacology February 19, 2010
- DARK Classics in Chemical Neuroscience: NBOMes ACS Chemical Neuroscience October 28, 2019
- Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action Handbook of experimental pharmacology 2018
- LSD Administered as a Single Dose Reduces Alcohol Consumption in C57BL/6J Mice Frontiers in Pharmacology August 31, 2018
and 28 more in the library
Cites 16
- 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
- Effect of Ring Fluorination on the Pharmacology of Hallucinogenic Tryptamines Journal of Medicinal Chemistry October 19, 2000
- Neuropharmacological reassessment of the discriminative stimulus properties ofd-lysergic acid diethylamide (LSD) Psychopharmacology 1987
- Characterization of the Discriminative Stimulus Properties Induced by 5‐HT1and 5‐HT2Agonists in Rats Pharmacology & Toxicology February 1, 1989
and 11 more in the library