Antagonism of the LSD cue by putative serotonin antagonists: relationship to inhibition of in vivo [3H]spiroperidol binding.

In two groups of rats trained to discriminate 0.08 or 0.16 mg/kg of lysergic acid diethylamide (LSD) from saline, pirenperone and ketanserin completely blocked the stimulus effect of LSD. Pizotifen (BC-105) blocked the LSD cue when the training dose was 0.08 mg/kg, but had variable effects in the 0.16 mg/kg of LSD-trained group. The antagonism of the 0.08 mg/kg cue occurred at doses of the antagonists which blocked [3H]spiroperidol labeled 5-HT2 receptors in the frontal cortex in vivo; binding in the striatum was unaffected by the LSD antagonists. However, in doses which produce the LSD cue, neither LSD nor the 5-HT agonist, 5-methoxy-N,N-dimethyltryptamine, which substitutes for LSD, inhibited the binding in either the cortex or the striatum. The results are discussed in relation to the possible neuropharmacological basis for the LSD cue.