Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT(1A) receptor knockout mice: implications for schizophrenia.
Maarten Van den Buuse, Emma Ruimschotel, Sally Martin, Victoria B Risbrough, Adam L. Halberstadt
Neuropharmacology 2011 DOI: 10.1016/j.neuropharm.2011.04.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | 5-HT(1A) receptor knockout mice |
| Interventions | Amphetamine MK-801 5-methoxy-N N-dimethyltryptamine (5-MeO-DMT) apomorphine |
| Topics | 5-MeO-DMT DMT Serotonin |
| Keywords | Schizophrenia research Psychosis model Mental health Brain disorders Serotonin receptors 5-ht1a receptor Neuroreceptors Brain chemistry Dopamine modulation Amphetamine response Hyperactivity Neurotransmitters Hallucination mechanisms Hallucinogen effects Perception Brain function |
| Citations | 37 |
| Key points | 5-HT(1A) receptor knockout mice displayed enhanced hyperactivity to amphetamine but reduced response to a hallucinogen, with no changes in NMDA-related or sensory gating measures. |
Abstract
Serotonin-1A (5-HT(1A)) receptors may play a role in schizophrenia and the effects of certain antipsychotic drugs. However, the mechanism of interaction of 5-HT(1A) receptors with brain systems involved in schizophrenia, remains unclear. Here we show that 5-HT(1A) receptor knockout mice display enhanced locomotor hyperactivity to acute treatment with amphetamine, a widely used animal model of hyperdopaminergic mechanisms in psychosis. In contrast, the effect of MK-801 on locomotor activity, modeling NMDA receptor hypoactivity, was unchanged in the knockouts. The effect of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) was markedly reduced in 5-HT(1A) receptor knockout mice. There were no changes in apomorphine-induced disruption of PPI, a model of sensory gating deficits seen in schizophrenia. Similarly, there were no major changes in density of dopamine transporters (DAT) or dopamine D(1) or D(2) receptors which could explain the behavioural changes observed in 5-HT(1A) receptor knockout mice. These results extend our insight into the possible role of these receptors in aspects of schizophrenia. As also suggested by previous studies using agonist and antagonist drugs, 5-HT(1A) receptors may play an important role in hallucinations and to modulate dopaminergic activity in the brain.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cited by 15
- Effect of Hallucinogens on Unconditioned Behavior Current Topics in Behavioral Neurosciences 2016
- A narrative synthesis of research with 5-MeO-DMT. Journal of Psychopharmacology March 1, 2022
- The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs. The International Journal of Neuropsychopharmacology August 1, 2014
- Serotonergic hallucinogens as translational models relevant to schizophrenia The International Journal of Neuropsychopharmacology August 13, 2013
- The serotonin hallucinogen 5-MeO-DMT alters cortico-thalamic activity in freely moving mice: Regionally-selective involvement of 5-HT1A and 5-HT2A receptors. Neuropharmacology November 1, 2018
and 10 more in the library
Cites 7
- Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice Journal of Psychopharmacology December 8, 2010
- Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors. Psychopharmacology November 1, 2008
- Hallucinogens. Pharmacology & Therapeutics February 1, 2004
- Serotonin and schizophrenia Handbook of Behavioral Neuroscience 2020
- 5-HT_2A and 5-HT_2C Receptors Exert Opposing Effects on Locomotor Activity in Mice Neuropsychopharmacology July 1, 2009
and 2 more in the library