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-HT2A 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 D2-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.