A Kappa Opioid Model of Atypical Altered Consciousness and Psychosis: U50488, DOI, AC90179 Effects on Prepulse Inhibition and Locomotion in Mice
Michael A Ruderman, Susan B Powell, Mark A. Geyer
Journal of young investigators July 1, 2009
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Measures | prepulse inhibition (BPM) measures |
| Topics | Altered states of consciousness |
| Key findings | Kappa opioid activation-induced effects on sensorimotor gating were reversed by serotonin 2A deactivation, suggesting kappa opioid system involvement in altered states of consciousness and potential as an atypical antipsychotic or screening tool. |
Abstract
Sensorimortor gating and locomotion are behaviors that reflect pre-attentive sensory filtering and higher order, top-down, sensory processing, respectively. These processes are thought to affect either the perception of novelty in an environment (filtering) or cognition (higher order processing), salient features of models of altered states of consciousness (ASC). Drugs with highly selective receptor affinities that produce ASC can help to establish neural correlates, pathways, and mechanisms underlying ASC. Furthermore, screening for substances that selectively reverse drug-induced sensory processing departures is valuable for development of experimental antipsychotics. This study investigated the anomalous opioid sub-type, the kappa opioid (KA) system, within the two ASC models. Significant interaction and reversal effects between KA and the serotonin/2A (5-HT2A) system – the serotonin sub-type associated with classical psychedelics – were observed in three BPM measures. These measures showed that KA activation-induced effects could be reversed by 5-HT2A deactivation. These results suggest that KA could function as an atypical antipsychotic medications and/or as a screening tool for new antipsychotic medicines. The experimental work for this study comprised dose-response and reversal experiments with drugs that activate and deactivate kappa opioid and serotonin systems in the two behavioral models for the first time in mice.
Comparable studies
Other preclinical and animal studies on altered states of consciousness, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Varieties of the Psychedelic Experience: A Preliminary Study of the Association Between the Reported Subjective Effects and the Binding Affinity Profiles of Substituted Phenethylamines and Tryptamines | 2018 | Observational study combining in vitro binding data with natural language processing of user reports | |
| Topological Analysis of Differential Effects of Ketamine and Propofol Anesthesia on Brain Dynamics Macaques | 2020 | Experimental neuroscience | n = 2 |