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

Abstract

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.