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Kuhn DM, White FJ, Appel JB.
“The Discriminative Stimulus Properties of LSD: Mechanisms of Action”.
Neuropharmacology. 1978;17(4-5):257-63.
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Abstract
The mechanisms of action of the discriminative stimulus properties of LSD were studied. 36 Male albino Sprague-Dawley rats (250-300 g) were trained to discriminate d-LSD from saline in 2-lever-operant chambers. Behavioral training and injections of saline of LSD (0.08 mg/kg, i.p.) were continued on a double alternation sequence until the animals were able to respond to the correct lever in a 2-lever chamber. The following drugs were then given alone and with LSD, before testing for lever choice: L-tryptophan 100 mg/kg (TRY), or imipramine 5 mg/kg (CMI), fluoxetine 10 mg/kg (Lilly), quipazine 2.5 mg/kg (Miles-Ames), methiothepin 0.28-2.8 mcmol/kg (MTP; Roche), cyproheptadine 1.4-11.2 mcmol/kg (CYP; Merck USA), methysergide 5.6-11.2 mcmol/kg (UML; Sandoz-Wander), 2-bromo-D-lysergic acid diethylamide 1.4-2.8 mcmol/kg, apomorphine 0.5 or 1 mg/kg, haloperidol 0.7 or 1.4 mcmol/kg (McNeil), fluphenazine 2.8 or 5.6 mcmol/kg (Squibb), tritluoperazine 1.4, 2.8 or 5.6 mcmol/kg (SK+F), a-flupenthixal 0.7 or 1.4 mol/kg (Lund beck), (+)-butaclamol 0.7 or 1.4 mcmol/kg (Ayers"), phentolamine 10 mg/kg, propranolol 20 mg/kg, atropine 2 mg/kg and promethazine 3 mg/kg. Results After injections of TRY, CMI or fluoxetine (alone) the response choice was primarily on the saline lever; when these were given with LSD, they did not reduce the discriminability. Quipazine produced a significant transfer to LSD. MTP, CYP, UML and cinanserin (11.2-33.6 mol/kg) reversed the LSD cue in a dose-related manner. Apomorphine produced a partial transfer to LSD. DA antagonists, a and §-adrenergic, cholinergic and histaminergic antagonists were all without effect on the discriminability of LSD. The discriminative stimulus properties of LSD may be mediated by post-synaptic serotonin or LSD receptors. Dopamine receptors do not seem to be involved in the LSD stimulus cue.
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