Psychopharmacology

, Volume 60, Issue 3, pp 281–289 | Cite as

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
Original Investigations

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.

Key words

Denervation Dihydroxytryptamines Muscle spasms Myoclonus Serotonin Super-sensitivity 

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Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • R. Malcolm Stewart
    • 1
  • Alexander Campbell
    • 1
  • Günther Sperk
    • 1
  • Ross J. Baldessarini
    • 1
  1. 1.Mailman Laboratories for Psychiatric Research, McLean Division of Massachusetts General Hospital, and Departments of Psychiatry and NeurologyHarvard Medical SchoolBostonUSA

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