Further evidence that the delayed temporal dopaminergic effects of LSD are mediated by a mechanism different than the first temporal phase of action

Pharmacol Biochem Behav. 2007 Oct;87(4):453-61. doi: 10.1016/j.pbb.2007.06.001. Epub 2007 Jun 14.

Abstract

Activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic effects of LSD. Nevertheless, in a previous report we provided evidence that a delayed temporal phase of the behavioral pharmacology of LSD is mediated by D(2)-like dopamine receptor stimulation. In this study rats were trained to discriminate LSD with either a 30 min preinjection time (LSD-30, N=12) or a 90 min preinjection time (LSD-90, N=13) from saline, using a two-lever, food-reinforced operant conditioning task. We then tested a large number of agonists and antagonists belonging to distinct pharmacological classes in these animals. As anticipated, classical hallucinogens such as psilocin and mescaline substituted only in LSD-30 rats, and not in LSD-90 rats. The dopamine receptor agonists ABT-724, aripiprazole, dihydrexidine, WAY 100635, and SKF 38393, fully or partially mimicked LSD-90, but not LSD-30. The results reported here support and extend our previous conclusion that the delayed temporal effects of LSD are mediated by activation of a dopaminergic system.

MeSH terms

  • Animals
  • Conditioning, Operant / drug effects
  • Data Interpretation, Statistical
  • Discrimination Learning / drug effects
  • Dopamine / physiology*
  • Dopamine Agonists / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Food
  • Hallucinogens / pharmacology*
  • Lysergic Acid Diethylamide / pharmacology*
  • Male
  • Neurotransmitter Agents / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A / drug effects
  • Serotonin Receptor Agonists / pharmacology*

Substances

  • Dopamine Agonists
  • Hallucinogens
  • Neurotransmitter Agents
  • Receptor, Serotonin, 5-HT2A
  • Serotonin Receptor Agonists
  • Lysergic Acid Diethylamide
  • Dopamine