Blockade of the behavioral effects of lysergic acid diethylamide, 2,5- dimethoxy-4-methylamphetamine, quipazine and lisuride by 5- hydroxytryptamine antagonists

DJ Mokler, RL Commissaris, MR Warner and RH Rech

The effects of lysergic acid diethylamide (LSD), 2,5-dimethoxy-4- methylamphetamine (DOM), quipazine or lisuride alone and in combination with the 5-hydroxytryptamine antagonist metergoline, pizotifen and cinanserin were studied in rats responding on a fixed-ratio 40 schedule of food presentation. LSD, DOM, quipazine or lisuride produced a similar dose-dependent decrease in the number of food presentations (ED50 values: 81 micrograms/kg, 0.6 mg/kg, 1.6 mg/kg and 31 micrograms/kg, respectively) and a reciprocal increase in the number of pause intervals (IRTs = 10 sec). All three antagonists attenuated the behavioral effects of LSD and DOM for both food presentations and pause intervals. The LSD-response curve for reinforcers was shifted to the greatest degree by pizotifen (1.0 mg/kg), followed by cinanserin (20 mg/kg) and metergoline (1.0 mg/kg). The ED50 values for this effect were 334, 181 and 141 micrograms/kg, respectively. The DOM dose- response pattern for decrease in reinforcers was shifted to the greatest degree by metergoline, followed by pizotifen and cinanserin (ED50 values: 26.5, 3.2 and 1.8 mg/kg, respectively). The effect of quipazine on reinforcers was antagonized by metergoline and pizotifen (ED50 values: greater than 8.0 for both) but not by cinanserin, although all three antagonists attenuated the increase in pause intervals in the same order as they did for DOM. The decrease in reinforcers by lisuride was equally antagonized by metergoline and pizotifen (ED50 values: 58 and 57 micrograms/kg, respectively), whereas cinanserin potentiated the effect of lisuride (ED50: 16 micrograms/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 227, Issue 3, pp. 557-562, 12/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics