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Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the

Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the

  1. ThirdEyeFloond
    Psychopharmacology
    DOI 10.1007/s00213-008-1238-0

    Danuta Marona-Lewicka & Benjamin R. Chemel &
    David E. Nichols

    Rationale: Lysergic acid diethylamide (LSD) differs from other types of hallucinogens in that it possesses direct dopaminergic effects. The exact nature of this component has not been elucidated.
    Objective: The present study sought to characterize the effects of several dopamine D4 agonists and antagonists on the discriminative stimulus effect of LSD at two pretreatment
    times and 2,5-dimethoxy-4-iodoamphetamine (DOI), a selective 5-HT2A/2C agonist.
    Materials and methods: Male Sprague–Dawley rats were trained in a two-lever, fixed ratio (FR) 50, food-reinforced task with LSD-30 (0.08 mg/kg, i.p., 30-min pretreatment time), LSD-90 (0.16 mg/kg, i.p., 90-min pretreatment time), and DOI (0.4 mg/kg, i.p., 30-min pretreatment time) as
    discriminative stimuli. Substitution and combination tests with the dopamine D4 agonists, ABT-724 and WAY 100635, were performed in all groups. Combination tests were run using the dopamine D4 antagonists A-381393 and L-745,870 and two antipsychotic drugs, clozapine and olanzapine.
    Results: WAY 100635 produced full substitution in LSD-90 rats, partial substitution in LSD-30 rats, and saline appropriate responding in DOI-trained rats. ABT-724 partially mimicked the LSD-90 and LSD-30 cues, but produced no substitution in DOI-trained rats. In combination tests, both agonists shifted the dose–response curve of LSD leftward, most potently for the LSD-90 cue. The D4
    antagonists significantly attenuated both the LSD-90 and LSD-30 cue, but had no effect on the DOI cue.
    Conclusion Dopamine D4 receptor activation plays a significant modulatory role in the discriminative stimulus effects in LSD-90-trained rats, most markedly for the later temporal phase of LSD, but has no effect on the cue produced by DOI.