The excitability and rhythm of medullary respiratory neurons in the cat are altered by the serotonin receptor agonist 5-methoxy-N,N, dimethyltryptamine.
Brain research June 13, 1994 DOI: 10.1016/0006-8993(94)91909-7 via PubMed
Summary
AI-generated from the abstract5-MeO-DMT, a compound that activates serotonin receptors, had two distinct effects on brainstem respiratory neurons in cats. Larger doses (43 ± 8.9 μg/kg) silenced these neurons by hyperpolarizing them, an effect reduced by a serotonin receptor blocker given intravenously but not locally. Smaller doses (27 ± 2.78 μg/kg) increased the firing rate of both inspiratory and expiratory neurons, making inspiratory bursts shorter and expiratory bursts start earlier relative to breathing rhythm. The larger-dose depression appears to involve both presynaptic network effects and postsynaptic activation of 5HT-1A receptors, while the smaller-dose excitation likely results from binding to 5HT-1A receptors on early inspiratory neurons.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Cats |
| Interventions | 5-MeODMT cinanserin |
| Dose | 43 ± 8.9 micrograms/kg i.v. (higher), 27 ± 2.78 micrograms/kg i.v. (lower) |
| Citations | 37 |
| Key finding | 5-MeO-DMT has dose-dependent, opposing effects on medullary respiratory neurons: larger doses suppress firing via presynaptic and postsynaptic 5HT-1A receptor activation, while smaller doses increase neuronal discharge and alter respiratory timing. |
Abstract
5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) is an indolealkylamine which has agonist activity at 5HT receptors. In the present investigation, 5-MeODMT had two types of effects on medullary respiratory neurons of the cat. Iontophoretic administration or i.v. doses (43 +/- 8.9 micrograms/kg) of 5-MeODMT hyperpolarized respiratory neurons and severely reduced action potential discharges. Cinanserin, a 5HT-2/1 c receptor antagonist, when injected i.v. reduced the inhibition produced by i.v. injection of 5-MeODMT. Iontophoresis of cinanserin did not antagonize inhibition produced by iontophoresis of 5-MeODMT or 5-HT. The depression of respiratory discharge by i.v. injection of 5-MeODMT is attributed to presynaptic effects (network depression) and post-synaptic activation of 5HT-1A receptors on respiratory neurons. 5-MeODMT (27 +/- 2.78 micrograms/kg i.v.) also increased discharge frequency of inspiratory and expiratory neurons. Inspiratory neuron discharges were briefer and expiratory neuron discharges occurred earlier in relation to phrenic nerve activity. It is suggested that the effects of the smaller doses are due to binding of 5-MeODMT to 5HT-1A receptors on early inspiratory neurons of the medulla.