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 DOI: 10.1016/s0022-3565(25)30534-3 via OpenAlex
Summary
AI-generated from the abstractLSD and DMT disrupt food-rewarded bar pressing in rats in a dose-dependent manner. Adult male Holtzman rats trained to press a bar for milk on a fixed-ratio schedule received daily injections of DMT (3.2 or 10 mg/kg) every 2 hours for 21 days. Bar pressing worsened progressively during the first week, with the 10 mg/kg group ceasing to press by day 6, but gradually recovered with continued injections. Rats given 3.2 mg/kg DMT showed cross-tolerance to LSD (0.1 mg/kg). Conversely, rats made tolerant to LSD over 21 days did not initially show cross-tolerance to 10 mg/kg DMT, but after additional LSD injections until complete tolerance, they displayed cross-tolerance to 3.2 mg/kg DMT.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult male Holtzman rats |
| Interventions | DMT LSD |
| Dose | 3.2 or 10 mg/kg DMT; 0.1 mg/kg LSD |
| Duration | 21 days of chronic DMT injections; 21 days plus 4 days of three-times-daily injections for LSD tolerance induction |
| Topics | LSD |
| Keywords | Cross-tolerance Bar unit Food delivery Animal science |
| Citations | 33 |
| Key finding | Chronic DMT treatment produces tolerance to its disruptive effects on bar pressing, and cross-tolerance between DMT and LSD is asymmetrical, depending on the dosing regimen. |
Abstract
Lysergic acid diethylamide=25 (LSD) and N,N-dimethyltryptamine (DMT) abolish food-rewarded, fixed-ratio bar pressing by rats in a dose-related fashion. Adult male Holtzman rats trained to press a bar (respond) for milk reward on a 4-response fixed-ratio schedule were given i.p. injections of 3.2 or 10 mg/kg of DMT every 2 hours for 21 days. Every 24 hours the animals were placed in operant chambers for 30 minutes before a scheduled injection and were left in the chambers for 30 to 80 minutes after. During the first week of chronic treatment, daily bar pressing worsened progressively until the 6th day of the series, at which time rats in the 10 mg/kg group did not bar press at all. As the chronic injections continued, rates of bar pressing gradually increased until responding was not disrupted at all by an injection of DMT. Rats in the 3.2 mg/kg group showed cross-tolerance to an injection of LSD (0.1 mg/kg). Another group of rats was made partially tolerant to the disruptive effects of LSD (0.1 mg/kg i.p.) on bar pressing with a series of injections given once per day for 21 days and then three times per day for the next 4 days. Cross tolerance was not demonstrated to a challenge injection of 10 mg/kg of DMT. The LSD injections were continued for another 3 to 5 days until the animals were completely tolerant to the LSD. They then displayed cross-tolerance to 3.2 mg/kg of DMT.