The selective 5-HT2A receptor antagonist MDL 100,907 counteracts the psychomotor stimulation ensuing manipulations with monoaminergic, glutamatergic or muscarinic neurotransmission in the mouse--implications for psychosis.
Journal of neural transmission. General section 1995 DOI: 10.1007/bf01276460 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Monoamine-depleted mice and intact mice |
| Interventions | MK-801 LSD atropine clonidine UH-232 MDL 100 907 apomorphine GBR 12 909 |
| Dose | subthreshold dose of MK-801, subthreshold dose of LSD |
| Topics | Serotonin |
| Key findings | Subthreshold doses of MK-801 and LSD together produced marked locomotor stimulation in monoamine-depleted mice, and MK-801, atropine, or clonidine acted synergistically with the 5-HT2 agonist UH-232 to produce locomotor activation. The selective 5-HT2A antagonist MDL 100,907 blocked these effects but not hyperactivity from other drug combinations, suggesting a "permissive" role for 5-HT2 receptors in psychomotor activation and possible relevance for antipsychotic therapy. |
Abstract
The present study has shown that a subthreshold dose of the uncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801, combined with a subthreshold dose of LSD, produces marked locomotor stimulation in monoamine-depleted mice. Likewise, MK-801, as well as the muscarine receptor antagonist atropine and the alpha-adrenoceptor agonist clonidine, were found to interact synergistically with the putative 5-HT2 receptor agonist UH-232 to produce locomotor activation in monoamine-depleted mice. All these responses were effectively blocked by the highly selective 5-HT2A receptor antagonist MDL 100,907. On the other hand, MDL 100,907 did not antagonize the hyperactivity response produced by clonidine given in combination with MK-801 or atropine in monoamine-depleted mice, nor the response produced by the mixed DA receptor agonist apomorphine, underlining the selectivity in the antagonistic action of MDL 100,907. Furthermore, MDL 100,907 attenuated the hyperactivity produced in intact mice by such disparate agents as MK-801, atropine or the DA uptake inhibitor GBR 12,909. A putative "permissive" role of the 5-HT2 receptor in the context of psychomotor activation is discussed, as well as its possible importance as target for antipsychotic therapy.