Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis.
Danuta Marona‐lewicka, Ronald A Thisted, David E Nichols
Psychopharmacology July 2005 DOI: 10.1007/s00213-005-2183-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Sample size | 25 |
| Population | Male Sprague-Dawley rats |
| Intervention | LSD |
| Dose | 186 nmol/kg (0.08 mg/kg) and 372 nmol/kg (0.16 mg/kg), i.p. |
| Topics | LSD |
| Key findings | LSD's discriminative stimulus in rats occurs in two phases: an early phase mediated by 5-HT2A receptors and a later phase mediated by D2 dopamine receptors. The later phase was inhibited by haloperidol and substituted by D2 agonists, supporting a dopaminergic mechanism. |
Abstract
The effect of LSD in humans has been described as occurring in two temporal phases. The behavioral effects in rats also occur in two temporal phases: an initial suppression of exploration followed by increased locomotor activity. We decided to investigate this phenomenon from the perspective that the pharmacology might have relevance to the neurochemical mechanisms underlying psychosis. Twenty-five male Sprague-Dawley rats were trained to discriminate LSD (186 nmol/kg, 0.08 mg/kg, i.p.) with a 30-min preinjection time (LSD-30, N=12) and LSD (372 nmol/kg, 0.16 mg/kg, i.p.) with a 90-min preinjection time (LSD-90, N=13) from saline, using a two-lever, food-reinforced operant conditioning task. LSD (186 or 372 nmol/kg, 0.08 or 0.16 mg/kg) given 30 min prior to training produced a cue that was completely antagonized by 5-HT2A antagonists and lasted no longer than 1 h. LSD (372 nmol/kg, 0.16 mg/kg) injected 90 min before training produced a cue that was not fully blocked by 5-HT2A antagonists, but instead was significantly inhibited by haloperidol. In these rats, substitution no longer occurred with the 5-HT2 agonists DOI or LSD (30 min preinjection), but full substitution was obtained with the D2 agonists apomorphine, N-propyldihydrexidine, and quinelorane. The discriminative stimulus effect of LSD in rats occurs in two phases, and these studies provide evidence that the later temporal phase is mediated by D2 dopamine receptor stimulation. A second temporal phase that involves dopaminergic pathways would be consistent with the widespread belief that excessive dopaminergic activity may be an underlying cause of paranoid psychosis.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
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- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Effective connectivity changes in LSD-induced altered states of consciousness in humans. Proceedings of the National Academy of Sciences January 28, 2019
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
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and 14 more in the library