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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46430/1/213_2004_Article_BF00432112.pd

Effects of selected opioid agonists and antagonists on DMT-and LSD-25-induced disruption of food-rewarded bar pressing behavior in the rat

Several opioid agonists and antagonists interact 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 schedule, i.e., a reward of 0.01 ml sugar-sweetened milk was earned on every fourth bar press. DMT (3.2 and 10.0 mg/kg) and LSD (0.1 mg/kg) given IP with 0.9% NaCl pretreatment, disrupted food-rewarded FR4 bar pressing. Animals were pretreated IP (10–15 min) with predetermined, behaviorally noneffective doses of morphine, methadone, naltrexone, and the (+)-and (-)-enantiomers of naloxone prior to receiving DMT or LSD. Dose-dependent effects were shown with opioid agonist pretreatment. Morphine (0.32–1.0 mg/kg) and methadone (0.32 mg/kg) significantly antagonized the bar pressing disruption induced by DMT and LSD. Larger doses of morphine (3.2 mg/kg) and methadone (1.0–3.2 mg/kg) potentiated only LSD-induced effects, with no effect on DMT-treated groups. The opioid antagonists (-)-naloxone and naltrexone potentiated the disruption of bar pressing induced by DMT and LSD. Failure of (+)-naloxone to potentiate the DMT effects was attributed to a stereospecific opioid antagonist effect of (-)-naloxone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46425/1/213_2004_Article_BF00432428.pd