Further evidence that the delayed temporal dopaminergic effects of LSD are mediated by a mechanism different than the first temporal phase of action.
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.
Marona-Lewicka
Danuta
D
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, RHPH, 575 Stadium Mall Dr. Purdue University, West Lafayette, IN 47907-2091, United States.
Nichols
David E
DE
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004193:Discrimination Learning / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005502:Food; D006213:Hallucinogens / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D018491:Dopamine Agonists; D006213:Hallucinogens; D018377:Neurotransmitter Agents; D044402:Receptor, Serotonin, 5-HT2A; D017366:Serotonin Receptor Agonists; D008238:Lysergic Acid Diethylamide; D004298:Dopamine