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 January 1, 2011 DOI: 10.1016/j.neuropharm.2011.04.001 via PubMed
Summary
AI-generated from the abstractMice lacking the serotonin-1A (5-HT(1A)) receptor showed enhanced hyperactivity in response to amphetamine, a model of the hyperdopaminergic state linked to psychosis. The response to MK-801, which models NMDA receptor hypoactivity, was unchanged. The effect of the hallucinogen 5-MeO-DMT was markedly reduced in the knockout mice. No changes were seen in sensory gating deficits induced by apomorphine, nor in the density of dopamine transporters or D1/D2 receptors. These results suggest that 5-HT(1A) receptors play a role in hallucinations and modulating dopamine activity, extending insight into their possible involvement in schizophrenia.
Study at a glance
| 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 |
| Keywords | Schizophrenia research Psychosis model Mental health Brain disorders Serotonin receptors |
| Citations | 37 |
| Key finding | 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.