Observational Determination of Dose-Response Curves in Hallucinogen-Treated Monkeys

Abstract

An objective behavioral profile that was previously shown to distinguish the effects of hallucinogens from those of other classes of drugs was used here to further study hallucinogenic behaviors. Saline, d-amphetamine sulfate and five doses of dimethyltryptamine (DMT) were administered to solitary adolescent rhesus monkeys in a totally dark environment and their behavior was observed via infrared monitors, videotaped, and scored in a number of categories. Scores in the following categories systematically increased with ascending doses of DMT: exploration, locomotion, stereotypy, spasm, tracking and duration of inappropriate behavior. In addition, some behaviors sensitive to hallucinogens occurred with greater frequency in the dark than in a previous study conducted in the light. Behaviors such as tracking and fear grimaces, usually associated with specific stimuli, emerged in the absence of such stimuli in the dark. These results suggested hallucinogen-induced changes in perceptual-motor systems, if not hallucinations per se.

Chronic, Intermittent Microdoses of the Psychedelic N,N-Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents

“…First, DMT constitutes the core structure of all indole-containing psychedelics including LSD and psilocybin . Second, DMT is known to impact rodent behaviors relevant to mood, anxiety, cognitive function, and sociability. ,− Third, DMT is the principal psychoactive component in ayahuasca, an Amazonian tisane typically administered on a chronic, intermittent schedule that has been shown to have antidepressant effects . Additionally, we have previously demonstrated that an acute hallucinogenic dose of DMT (10 mg/kg) administered to rats produces robust behavioral phenotypes in several paradigms relevant to mood and anxiety disorders, enabling us to compare the effects of a single high dose of the compound to those produced by chronic, intermittent, low doses of the drug.…”

Preclinical and translational models for delirium: Recommendations for future research from the NIDUS delirium network

“…Although these behaviors can be challenging to interpret in rodents (see preceding discussion), human-like hallucinatory and locomotor behaviors are often present in NHP models. [108][109][110] Further, reliable cognitive task performance that enables testing of attention, altered levels of consciousness, and disorientation is possible in NHP, [104][105][106] and NHP have demonstrated that recordings of EEG across the neocortex is comparable to those seen in humans. 111,112 Evoked potentials…”

“…To establish EEG markers for all types of delirium including hyperactive and mixed type, it will be essential to demonstrate temporal correlations between these markers and delirium behaviors in the model. Although these behaviors can be challenging to interpret in rodents (see preceding discussion), human‐like hallucinatory and locomotor behaviors are often present in NHP models 108‐110 . Further, reliable cognitive task performance that enables testing of attention, altered levels of consciousness, and disorientation is possible in NHP, 104‐106 and NHP have demonstrated that recordings of EEG across the neocortex is comparable to those seen in humans 111,112 …”