Interaction of synthetic opioid metenkephalin peptide analogs, Lilly 127623 and FK 33-824 with indole hallucinogens: antagonism of N,N-dimethyltryptamine- and LSD-induced disruption of food-rewarded bar pressing behavior in the rat.

The selected opioid metenkephalin synthetic peptide analogs Lilly (LY) 127623 and FK 33-824 were tested for behavioral dose effects and potential interaction with N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) in adult male Holtzman rats trained on a positive reinforcement fixed-ratio 4 (FR-4) behavioral bar pressing schedule, i.e., a reward of 0.01 ml sugar-sweetened evaporated milk was earned on every fourth bar press. DMT (3.2 mg/kg) and LSD (0.1 mg/kg), administered IP following a 0.9% NaCl 15-20-min control pretreatment, disrupted established food-rewarded FR-4 bar pressing in a consistent and reproducible manner. Animals pretreated IP with predetermined behaviorally noneffective doses of LY 127623 (0.01-0.32 mg/kg) and FK 33-824 (0.001-0.01 mg/kg) 15-20 min prior to receiving DMT demonstrated significant antagonism to DMT-induced disruption of FR-4 bar pressing, while doses of 0.10-0.32 mg/kg LY 127623 and 0.00032-0.0032 mg/kg FK 33-824 significantly antagonized LSD-induced behavioral effects.