A comparison of the stimulus effects of morphine and lysergic acid diethylamide (LSD)

Morphine and lysergic acid diethylamide (LSD) each was used as a discriminative stimulus for rats. After the injection of drug (morphine or LSD), depression of one lever of an operant test chamber resulted in positive reinforcement according to a variable interval schedule of 15 sec (VI-15 sec). When saline was given, responses on the opposite lever were reinforced. Discriminated responding occurred when either morphine or LSD served as the discriminative stimulus. When animals which were trained to d discriminate morphine from saline were given LSD, they pressed predominantly the saline-correct lever. Similarly, LSD discrimination did not generalize to morphine. Two 5-hydroxytryptamine (5-HT) antagonists, cyproheptadine and methysergide, and one acetylcholine (Ach) antagonist, atropine, did not effect morphine or LSD discrimination. The narcotic antagonist, naloxone, blocked the stimulus effect of morphine, but did not alter LSD discrimination. These results indicate that the morphine and LSD stimuli are dissimilar and that the integrity of 5-HT or Ach nervous systems is not essential for morphine or LSD to serve as a discriminative stimulus.