Behavioural Brain Research
December 1, 1995
Rick J. Strassman
257 citations
Dose-response data for the ultra-short-acting hallucinogen DMT were collected from experienced hallucinogen users. A new rating scale, the HRS, better resolved dose effects than biological measures. In a tolerance study with four closely spaced hallucinogenic doses, subjective responses showed no tolerance, while biological measures were inconsistently reduced, making DMT unique among classic hallucinogens for lacking tolerance to its psychological effects. A pindolol pre-treatment study found that pindolol significantly increased psychological responses to DMT, suggesting 5-HT1A agonism buffers 5-HT2-mediated psychedelic effects, opposite to findings in lower animal models.
Behavioural Brain Research
February 1, 2022
G. Northoff, Federico Zilio
138 citations
A review of the Temporo-spatial theory of consciousness (TTC) proposes that consciousness arises from the brain's spontaneous activity, not just from external stimuli. The TTC aims to bridge gaps between spontaneous and stimulus-related neural activity and between neuronal and phenomenal features. It introduces four mechanisms—expansion, globalization, alignment, and nestedness—linked to distinct dimensions of consciousness: phenomenal content, access, form/structure, and level/state. The authors conclude the TTC offers a unifying framework for different neuroscientific theories and generates empirically grounded hypotheses about the biological nature of consciousness and its relation to the brain.
Behavioural Brain Research
December 28, 2020
Anna U. Odland, Jesper L. Kristensen, Jesper T. Andreasen
60 citations
Psychedelic drugs that activate the 5-HT2A receptor show promise for treating psychiatric disorders like obsessive-compulsive disorder. In a mouse model of compulsive-like behavior (the marble burying test), the 5-HT2A receptor antagonist M100907 blocked the effect of the psychedelic DOI, and the 5-HT2C receptor antagonist SB242084 blocked the effect of citalopram, but neither antagonist blocked the effect of psilocybin. This confirms 5-HT2A receptor activation as a mechanism for reducing compulsive-like digging and suggests that 5-HT2A and 5-HT2C receptors can work in parallel. The results with psilocybin indicate that a mechanism independent of 5-HT2 receptors also contributes to its effect on repetitive digging.
Behavioural Brain Research
August 13, 2019
Andrew J. Polis, Paul J. Fitzgerald, Pho J. Hale et al.
58 citations
Ketamine has rapid antidepressant effects in many people with major depression, a major finding in psychopharmacology. Rodent studies from the 1990s laid the groundwork, and subsequent research includes human and reverse translational animal experiments. While rodent literature generally agrees ketamine has rapid and sustained antidepressant-like effects, disagreements exist over its precise mechanism. This review summarizes variable findings on mechanism, and differences in effects by dose, species, strain, test, stressor, and experimenter sex. Previously unpublished mouse strain data suggest subanesthetic ketamine lacks robust antidepressant-like properties in unstressed animals and may promote depression-like behavior. The data best support ketamine acting via NMDA receptor antagonism, transiently boosting glutamatergic signaling. Future studies should address stress sensitivity to better model human depression.
Behavioural Brain Research
October 1, 2021
A. Rafało-ulińska, A. Pałucha-poniewiera
46 citations
In a mouse model of chronic unpredictable mild stress, (R)-ketamine reduced anhedonia and apathy for up to seven days after a single dose, whereas (S)-ketamine's effects lasted only 24 hours to three days. (R)-ketamine's behavioral effects required activation of TrkB receptors, while (S)-ketamine's did not. (S)-ketamine activated mTOR and ERK pathways and increased GluA1 protein in the prefrontal cortex; (R)-ketamine increased mTOR expression without changing ERK phosphorylation. (S)-ketamine produced signs of possible side effects at the doses tested, while (R)-ketamine did not. These results suggest (R)-ketamine may be more effective, longer-lasting, and safer than (S)-ketamine.
Behavioural Brain Research
August 23, 2021
Carolina Aparecida Faria Almeida, Antônio Alves Pereira-Júnior, Jéssica Gonçalves Rangel et al.
33 citations
Repeated ethanol administration to mice produced behavioral sensitization, a model of alcohol use disorder. Subsequent daily treatment with ayahuasca (1.76 mg/kg DMT) for eight days attenuated that sensitization. Ayahuasca also reduced the anxiety-like behavior triggered by ethanol withdrawal and prevented ethanol-induced changes in 5-HT1a receptor and prodynorphin levels in the hippocampus, while reducing ethanol's effects on the dynorphin/prodynorphin ratio in the striatum. The results suggest ayahuasca may modulate neuroplastic changes caused by ethanol.
Behavioural Brain Research
July 14, 2022
Marina Goulart Da Silva, Guilherme Cabreira Daros, Fabiana Pereira Santos et al.
22 citations
Ayahuasca reduced anxiety-like and depressive-like behaviors in rats with neuroinflammation induced by lipopolysaccharide (0.63 mg/kg/mL). Eighty male rats, about 90 days old, were divided into control and LPS groups, with prevention and treatment subgroups. Ayahuasca (4 mL/kg) or saline was given by gavage one hour before or 24 hours after LPS or saline injections. Open field and forced swimming tests measured behavior. LPS rats given ayahuasca showed less anxiety-like behavior in both subgroups. Depressive-like behavior decreased in LPS rats given ayahuasca, in both prevention and treatment subgroups, compared to controls. The findings suggest anxiolytic and antidepressant potential of ayahuasca in neuroinflammation, possibly via antineuroinflammatory effects.
Behavioural Brain Research
November 6, 2020
Marina Goulart Da Silva, Guilherme Cabreira Daros, Rafael Mariano de Bitencourt
21 citations
Ayahuasca, a psychoactive decoction used for millennia by indigenous groups and Amazonian populations, shows therapeutic effects on behavioral disorders by inhibiting monoamine oxidase and activating serotonin receptors. Its pharmacological response also involves anti-inflammatory action, primarily through dimethyltryptamines (N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine), which regulate inflammation and immune homeostasis via sigma-1 receptors. Because neuroinflammation underlies many neurological and psychiatric diseases, the available evidence suggests ayahuasca is a promising and very safe therapeutic strategy, as extremely high doses are required for toxicity. However, additional studies are needed to confirm this evidence and fully elucidate the mechanisms involved.
Behavioural Brain Research
May 1, 2023
S. Kantor, Michael Lanigan, Lauren Giggins et al.
11 citations
Wistar-Kyoto (WKY) rats, a model of treatment-resistant depression, show increased REM sleep, fragmented sleep-wake patterns, and higher EEG delta power during non-REM sleep compared to Sprague-Dawley (SD) rats. Ketamine suppressed REM sleep and increased EEG gamma power during wakefulness in both strains, but the gamma increase was nearly twice as large in WKY rats. Ketamine also increased beta oscillations only in WKY rats. Plasma concentrations of ketamine and its metabolites were similar in both strains, suggesting the differences are not due to metabolism. These findings support acute REM sleep suppression as a measure of antidepressant responsiveness.
Behavioural Brain Research
April 1, 2022
Dimitri Daldegan‐bueno, Vanessa Manchim Favaro, Paulo Rogério Morais et al.
10 citations
Repeated daily ayahuasca administration over 30 days in male Wistar rats produced dose-dependent behavioral effects: a low dose (120 mg/kg) increased ambulation, while a very high dose (3600 mg/kg) decreased vertical exploration and reduced weight gain. The highest dose also increased c-Fos expression in the hippocampus and infralimbic cortex, indicating heightened neural activation in emotional processing and serotonergic pathways. The study does not support an anxiolytic effect of repeated ayahuasca in a novel anxiogenic environment but suggests low doses warrant further investigation. The absence of severe behavioral impairment reinforces ayahuasca's safety profile.
Behavioural Brain Research
February 10, 2026
Kristin A. Felsch, Jessica A. Siegel
MDMA is a psychomotor stimulant drug. Most research has focused on adults, but adolescence is a unique period of brain development where MDMA's effects may differ. This review summarizes 54 studies (48 in rodents, 6 in humans) on acute and repeated adolescent MDMA exposure. Acute high doses generally increase locomotor activity and impair the serotonin system. Repeated exposure shows conflicting results depending on dosing, testing environment, and timing. There is little research on adolescent females. More consistent dosing and female subjects are needed.