Receptor mechanisms in increased sensitivity to serotonin agonists after dihydroxytryptamine shown by electronic monitoring of muscle twitches in the rat
R. Malcolm Stewart, Alexander Campbell, Günther Sperk, Ross J. Baldessarini
Psychopharmacology 1979 DOI: 10.1007/bf00426669 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | L-5-hydroxytryptophan 5-methoxy-N N-dimethyltryptamine 5 7-dihydroxytryptamine desmethylimipramine cyproheptadine |
| Topics | Serotonin |
| Keywords | Denervation Dihydroxytryptamines Muscle spasms Myoclonus Super-sensitivity |
| Citations | 43 |
| Key findings | After serotonin neuron destruction with 5,7-DHT, rats showed dose-dependent myoclonus in response to serotonin precursors or agonists, which was blocked by serotonin antagonists and modulated by repeated drug exposure, suggesting postsynaptic receptor changes underlie behavioral supersensitivity. |
Abstract
Muscle twitches and autonomic changes were induced by systemic injections of L -5-hydroxytryptophan (5-HTP) or the serotonin agonist 5-methoxy- N,N -dimethyltryptamine (5-MeO-DMT) in rats previously lesioned with intracranial 5,7-dihydroxytryptamine (5,7-DHT) after desmethylimipramine. Movements were recorded sensitively and continuously by an electronic activity monitor. Spontaneous locomotor activity was strongly reduced after 5-HTP in both intact and lesioned rats, so that electronically recorded activity correlated very closely with disordered jerking movements scored by a behavioral rating scale. This myoclonus was dependent on the doses of 5-HTP and of 5,7-DHT and was strongly inhibited by serotonin antagonists. In lesioned rats, myoclonus occurred with unaltered activity of monoamine oxidase (MAO) and after only small increases in serotonin levels after 5-HTP, but even large increases in availability of serotonin in intact rats, or strong inhibition of serotonin uptake failed to induce myoclonus unless MAO was first inhibited. The response to 5-HTP in lesioned rats was attenuated by repeated injections of 5-HTP or 5-MeO-DMT. This decreased response was in turn blocked by repeated doses of a serotonin antagonist, but appeared not to be due to altered metabolism of 5-HTP or of serotonin; repeated pretreatment with cyproheptadine potentiated the myoclonic response to 5-HTP after DHT. Changes in postsynaptic receptors may be important in the behavioral supersentivity following 5,7-DHT, and restitution of serotonin or stimulation of its receptors after presynaptic denervation may suppress an evolving supersensitivity at receptive postsynaptic membranes.
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