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 |
| 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.