Some behavioral effects of hallucinogens are mediated by a postsynaptic serotonergic action: Evidence from single unit studies in freely moving cats

James Heym, Kurt Rasmussen, Barry L. Jacobs

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Although central serotonergic systems appear to be linked importantly to the mechanism of action of a variety of hallucinogenic drugs, the nature of this interaction has remained unclear. In the present study, the question of whether the critical link is presynaptic or postsynaptic was examined in cats. Behaviorally inactive doses (1.0 mg/kg) of the serotonin receptor antagonists mianserin, ketanserin or metergoline effectively blocked behavior, as measured by the cat limb flick response, elicited by either LSD (50 μg/kg) or DOM (250 μg/kg) but not that resulting either from lisuride (50 μg/kg) or a high dose of apomorphine (4 mg/kg). Pretreatment with 1.0 mg/kg of mianserin, which completely attenuated LSD's behavioral effect, failed to alter LSD-induced depression of mesencephalic serotonergic neuron discharge. These results demonstrate that at least some of the behavioral effects of LSD can be blocked by pharmacological antagonism of postsynaptic serotonin receptors which leaves LSD's presynaptic synaptic effect unaffected. Thus, the behavioral and possibly psychoactive, effects of hallucinogens appear to be attributable to an action at 5HT2 receptors, presumably located postsynaptically.

Original languageEnglish (US)
Pages (from-to)57-68
Number of pages12
JournalEuropean Journal of Pharmacology
Volume101
Issue number1-2
DOIs
StatePublished - May 18 1984

All Science Journal Classification (ASJC) codes

  • Pharmacology

Keywords

  • Cat behavior
  • Hallucinogens
  • Raphe unit activity
  • Serotonergic neurons
  • Serotonin antagonists
  • Serotonin receptors

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