Effects of selected opioid agonists and antagonists on DMT- and LSD-25-induced disruption of food-rewarded bar pressing behavior in the rat.
D M Ruffing, E F Domino
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.
Comparable studies
Other preclinical and animal studies on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Mice and cell lines | 2009 | Experimental study | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor Rats | 1971 | Experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study |
Citations in the library
Cited by 6
- Administration of N,N-dimethyltryptamine (DMT) in psychedelic therapeutics and research and the study of endogenous DMT Psychopharmacology January 22, 2022
- Effects of Psychedelics Lysergic Acid Diethylamide and R (–)-2,5-Dimethoxy-4-Iodoamphetamine on Oral Opioid Consumption and Naloxone-Precipitated Withdrawal in Male C57Bl/6J Mice Psychedelic Medicine March 28, 2026
- Antinociceptive effect of N,N-dimethyltryptamine (DMT) involving serotonergic, opioidergic, cannabinoidergic, and nitrergic systems in PGE2-induced hyperalgesia in rats Journal of Pain Research and Management February 14, 2026
- Opioid-hallucinogen interactions. Pharmacology, Biochemistry, and Behavior February 1986
- Involvement of the central serotoninergic system in the changes of leu-enkephalin level in discrete rat brain areas. Neuropeptides 1986
and 1 more in the library
Cites 7
- Lysergic acid diethylamide: evidence for stimulation of cerebral dopamine receptors Brain Research August 1, 1975
- Tolerance and limited cross-tolerance to the effects of N, N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) on food-rewarded bar pressing in the rat. Journal of Pharmacology and Experimental Therapeutics June 1, 1976
- Interaction between narcotic antagonist (naloxone) and lysergic acid diethylamide (LSD) in the rat Psychopharmacology 1977
- Naloxone potentiates the disruptive effects of mescaline on operant responding in the rat Pharmacology, Biochemistry, and Behavior October 1, 1980
- Lysergic acid diethylamide: Evidence for stimulation of pituitary dopamine receptors Psychopharmacology 1977
and 2 more in the library