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.