Naloxone alters the effects of LSD, DOM and quipazine on operant behavior of rats.
David J. Mokler, Randall L. Commissaris, J W Henck, Richard H. Rech
Pharmacology, Biochemistry, and Behavior September 1984 DOI: 10.1016/s0091-3057(84)80090-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical behavioral pharmacology experiment Peer reviewed |
|---|---|
| Population | Rats responding under a fixed-ratio 40 (FR-40) schedule of reinforcement |
| Interventions | d-lysergic acid diethylamide (LSD) 2 5-dimethoxy-4-methylamphetamine (DOM) quipazine naloxone |
| Dose | naloxone 4.0 mg/kg |
| Measures | fixed ratio (FR-40) response rates, 10-second pause intervals |
| Topics | LSD |
| Key findings | LSD, DOM, and quipazine each produced dose-dependent decreases in FR-40 response rates and increases in 10-second pause intervals. Naloxone (4.0 mg/kg) alone had no effect but potentiated the pause-producing effects of LSD and, to a lesser extent, DOM, while leaving quipazine's effect on reinforcers unchanged and slightly attenuating its pause effect. The authors propose these pause effects reflect activation of a selective portion of brain 5-HT receptors, with naloxone's potentiation possibly involving endogenous opioid modulation of central 5-HT systems. |
Abstract
Administration of the indolealkylamine hallucinogen d-lysergic acid diethylamide (LSD), the phenethylamine hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) and the putative 5-hydroxytryptamine (5-HT) agonist quipazine all produced a dose-dependent decrease in fixed ratio (FR-40) response rates and a concomitant increase in the number of 10-second pause intervals. Although naloxone (4.0 mg/kg) had no effect on FR-40 responding per se, the pause-producing effects of LSD and, to a lesser extent, DOM were potentiated by pretreatment with naloxone. The action of quipazine on reinforcers was unaffected by combination with naloxone, while the effect on pause intervals was slightly attenuated by naloxone pretreatment. These data and previous studies suggest that the pause-producing effects of indolealkylamine and phenethylamine hallucinogens reflect their activation of a selective portion of brain 5-HT receptors. The potentiation of these effects by naloxone may relate to a modulation of central 5-HT systems by endogenous opioid mechanisms tending to restore an imbalance in various 5-HT pathways caused by the hallucinogenic 5-HT agonists. The more generalized disruptive effects of quipazine on brain 5-HT systems may be less susceptible to the endogenous opioid modulation or may actually combine with it to induce a greater disruption.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 3
- 5HT-2 mediation of acute behavioral effects of hallucinogens in rats Psychopharmacology March 1, 1990
- Beating pain with psychedelics: Matter over mind? Neuroscience & Biobehavioral Reviews December 16, 2021
- The 5HT2 antagonist pirenperone reverses disruption of FR-40 by hallucinogenic drugs. Pharmacology, Biochemistry, and Behavior May 1985
Cites 11
- Behavioral sensitivity to LSD: Dependency upon the pattern of central 5HT depletion Pharmacology, Biochemistry, and Behavior May 1, 1977
- 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
- Antagonism of the behavioral effects of 2,5-dimethoxy-4-methylamphetamine (DOM) and quipazine by metergoline. Pharmacology, Biochemistry, and Behavior October 1981
- The behavioral effects of hallucinogens in rats following 5,7-dihydroxytryptamine administration into the medial forebrain bundle. Pharmacology, Biochemistry, and Behavior June 1981
and 6 more in the library