Effects of selected opioid agonists and antagonists on DMT- and LSD-25-induced disruption of food-rewarded bar pressing behavior in the rat.
Psychopharmacology 1981 DOI: 10.1007/bf00432428 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Adult male Holtzman rats trained on a positive reinforcement fixed ratio 4 (FR4) behavioral schedule |
| Interventions | DMT LSD morphine methadone naltrexone (-)-naloxone (+)-naloxone |
| Dose | DMT 3.2 and 10.0 mg/kg; LSD 0.1 mg/kg; morphine 0.32–1.0 mg/kg and 3.2 mg/kg; methadone 0.32 mg/kg and 1.0–3.2 mg/kg |
| Topics | DMT LSD |
| Key findings | Low doses of the opioid agonists morphine and methadone reduced the disruption of food-rewarded bar pressing caused by DMT and LSD, whereas higher agonist doses worsened only LSD's effects. The opioid antagonists naltrexone and (-)-naloxone increased the disruption from both drugs, and the failure of (+)-naloxone to do so is attributed to a stereo-specific opioid antagonist effect. |
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 (FR4) 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 stereo-specific opioid antagonist effect of (-)-naloxone.