LSD, 5-HT (serotonin), and the evolution of a behavioral assay

Neurosci Biobehav Rev. 2004 Jan;27(8):693-701. doi: 10.1016/j.neubiorev.2003.11.012.


Research in our laboratory, supported by NIDA and facilitated by Roger Brown, has indicated that serotonergic neuronal systems are involved in the discriminative stimulus effects of LSD. However, the only compounds that fully antagonize the LSD cue act at both serotonin (5-HT) and dopamine (DA) receptors. In addition, substitution for LSD in standard drug vs. no-drug (DND) discriminations does not necessarily predict either similar mechanisms of action or hallucinogenic potency because 'false positives' occur when animals are given drugs such as lisuride (LHM), quipazine, or, possibly, yohimbine. These effects can be greatly reduced by using drug vs. drug (D-D), drug vs. drug vs. no drug (D-ND), or drug vs. ' other' drug (saline, cocaine, pentobarbital) training procedures. Additional studies, in which drugs were administered directly into the cerebral ventricles or specific brain areas, suggest that structures containing terminal fields of serotonergic neurons might be involved in the stimulus effects of LSD.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Behavior / drug effects*
  • Discrimination, Psychological / drug effects*
  • Dopamine Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Humans
  • Lisuride / chemistry
  • Lisuride / pharmacology
  • Lysergic Acid Diethylamide / antagonists & inhibitors
  • Lysergic Acid Diethylamide / chemistry
  • Lysergic Acid Diethylamide / pharmacology*
  • Receptors, Serotonin / drug effects
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / pharmacology


  • Dopamine Agents
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin
  • Lysergic Acid Diethylamide
  • Lisuride