Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT1A receptor knockout mice: Implications for schizophrenia

Apr 20, 2011Neuropharmacology

Stronger amphetamine but weaker hallucinogen effects on movement in mice lacking a specific serotonin receptor: possible links to schizophrenia

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Abstract

5-HT(1A) receptor knockout mice show enhanced locomotor hyperactivity in response to amphetamine treatment.

Knockout of 5-HT(1A) receptors leads to increased activity in response to amphetamine, indicating a potential link to hyperdopaminergic mechanisms in psychosis.
The locomotor response to MK-801, which models NMDA receptor hypoactivity, remains unchanged in knockout mice.
Response to the hallucinogen 5-MeO-DMT is significantly reduced in 5-HT(1A) receptor knockout mice.
No significant changes are observed in apomorphine-induced disruption of sensory gating, a model relevant to schizophrenia.
Dopamine transporter density and dopamine D(1) or D(2) receptor levels do not differ in knockout mice, suggesting other mechanisms may underlie the behavioral changes.

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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.

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Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT1A receptor knockout mice: Implications for schizophrenia

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