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
January 1, 2013
Jonathan Cachat, Evan J. Kyzar, Christopher Collins et al.
112 citations
Ibogaine, a psychoactive compound from the iboga plant, alters multiple behaviors in adult zebrafish. At doses of 10 and 20 mg/L, it reversed the natural diving response, causing initial top swimming followed by bottom dwelling, and reduced the innate preference for dark environments. It did not change overall locomotion or wall-hugging behavior but altered spatial exploration, promoted mirror interaction, disrupted group cohesion, and induced color changes from melanophore aggregation. Brain c-fos expression and whole-body cortisol levels remained unchanged. These results demonstrate ibogaine's complex pharmacological profile and support the use of zebrafish for studying hallucinogenic drug effects.
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
November 16, 1994
S L Cappendijk, D Fekkes, M R Dzoljic
57 citations
In morphine-dependent rats, norharman (20 mg/kg) and ibogaine (40 mg/kg) each reduced the severity of withdrawal symptoms triggered by naloxone (4 mg/kg). Specific signs including teeth-chattering, chewing, penile licking, and diarrhea were lessened by both compounds. Norharman additionally decreased withdrawal-related grooming and rearing. The findings suggest that both norharman and ibogaine can inhibit opioid withdrawal syndrome.
Behavioural Brain Research
November 1, 1995
P Stoerig, A Cowey
54 citations
Consciousness is exclusive to living organisms that can distinguish self from non-self and voluntarily modify their behavior, requiring an intermediary neuronal net between sensory input and behavioral output. The visual system reveals two distinct aspects of consciousness: phenomenal vision (subjective experience) and conscious access (ability to retrieve and manipulate information). Blindsight patients, who process visual information without phenomenal vision, demonstrate this dissociation. Monkeys with striate cortex removal show similar absence of phenomenal vision, enabling further study of its neural basis. Conscious access likely requires higher cortical structures and depends on phenomenal representations, which may function to allow conscious thinking and planning.
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
May 1, 1996
S M Netto, F S Guimarães
45 citations
A compelling finding reveals that a systemic injection of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) can enhance exploration in an elevated plus maze after stress. In a study with rats, immediate post-stress treatment increased open arm exploration 24 hours later, while saline showed no effect. This enhancement was negated by pre-treatment with a selective 5-HT1A antagonist, suggesting that hippocampal 5-HT1A receptors play a critical role in mitigating the behavioral impacts of stress. These insights could inform future approaches to stress-related disorders.
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
February 1, 2021
Shane N Glackin, Tom Roberts, Joel Krueger
28 citations
Addiction involves causal factors at many levels—biomedical, neurological, social, and legal—making a simple reductive explanation unlikely. An integrative framework is needed to unify these diverse sciences while respecting their autonomy. The theory of 'Externalist' or '4E' cognition (extended, embodied, embedded, enactive) is proposed as such a framework, emphasizing the central role of the wider environment in mental processes. The paper outlines how this perspective applies to psychiatry generally, then dissolves the classic dichotomy between 'choice model' and 'disease model' of addiction, clarifies how an addict's brain interacts with her environment, and explains the success of some recovery strategies while suggesting new ones.
Behavioural Brain Research
October 1, 2020
Dionisio A Amodeo, Omron Hassan, Landon M. Klein et al.
25 citations
Activating serotonin 2A (5-HT2A) receptors impairs behavioral flexibility in male mice, as measured by a probabilistic reversal learning task. The selective 5-HT2A agonist 25CN-NBOH increased the number of trials needed to reach criterion during reversal learning, while the broader agonist DOI alone did not. However, combining DOI with a 5-HT2C receptor antagonist (SER-082) also impaired reversal learning, suggesting that 5-HT2A and 5-HT2C receptors have opposing effects on this aspect of executive function. All groups performed similarly on the initial spatial discrimination, indicating that the impairment was specific to adapting to changing contingencies.
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
December 1, 1997
J R Blackburn, K K Szumlinski
22 citations
Ibogaine may reduce dopamine activity only in animals or people previously exposed to addictive drugs, not in drug-naive ones. In three experiments with male Long Evans rats, 40 mg/kg ibogaine did not decrease preference for a sweet glucose + saccharin solution, nor did it attenuate conditioned flavor preference. However, ibogaine significantly lowered amphetamine-induced locomotion in rats that had received four prior doses of amphetamine, but not in drug-naive rats. The findings suggest ibogaine can reduce sensitized dopamine activity back toward baseline levels, potentially lowering drug craving in addiction.
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
July 14, 2017
Allan V. Kalueff, Aleksandra Kaluyeva, Émeline L. Maillet
21 citations
Noribogaine, the main psychoactive metabolite of ibogaine, produces robust anxiolytic-like behavior in adult zebrafish without affecting locomotion. In a 5-minute novel tank test following acute 20-minute immersion in 1, 5, or 10 mg/L noribogaine, treated fish spent more time and made more transitions to the top half compartment and showed fewer freezing bouts compared to controls. These results indicate noribogaine modulates components of the acute stress response related to emotionality and anxiety, suggesting it may be a potentially useful non-sedative anxiolytic agent.
Behavioural Brain Research
February 1, 2019
Arvie Abiero, Chrislean Jun Botanas, Leandro Val Sayson et al.
17 citations
5-MeO-AMT, a tryptamine used recreationally for its hallucinogenic and mood-elevating effects, triggers head-twitch response (HTR) in mice through activation of serotonin receptor 2a (5-HTR2a) in the prefrontal cortex. Acute administration at doses 0.3–10 mg/kg produced HTR, but repeated dosing led to tolerance. The 5-HTR2a antagonist ketanserin blocked the response. The drug increased 5-HTR2a mRNA and induced PKC-γ phosphorylation in the prefrontal cortex. 5-MeO-AMT did not produce locomotor sensitization, conditioned place preference, or self-administration, suggesting low abuse potential.
Behavioural Brain Research
February 25, 2023
Brianna F Roberts, Alexia L Zylko, Courtney E Waters et al.
13 citations
A single 1 mg/kg dose of psilocybin did not alter decision-making in probability or delay discounting tasks and did not reduce motivation in a progressive ratio task in healthy male and female rats. Psilocybin did produce the expected increase in head twitch responses, confirming the drug was pharmacologically active. These results suggest psilocybin may not impair or improve reward-based decision-making or motivation, indicating that its therapeutic effects in mental health disorders may not involve changes to brain systems underlying reward and decision-making. The findings also imply that widespread cognitive impairments may not occur even with chronic psilocybin treatment.
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
January 5, 2025
Khanyiso Bright Shangase, Mluleki Luvuno, Musa V Mabandla
6 citations
A double-hit model combining ketamine injections and social isolation in male rats produced stronger negative and cognitive symptoms of schizophrenia than either treatment alone. The isolated rats given ketamine showed high anxiety, elevated stress hormones (ACTH, corticosterone, norepinephrine), reduced social interaction, decreased oxytocin, increased aggression toward a juvenile intruder despite low testosterone, impaired visual learning and memory, and increased proinflammatory cytokines. The findings suggest that combining two schizophrenia-inducing interventions yields a more robust model for studying the neurobiological basis of negative and cognitive symptoms.
Behavioural Brain Research
May 8, 2025
Larissa da Silva Joaquim, Lara Rodrigues da Rosa, Yasmin Strickert et al.
5 citations
Ayahuasca, a decoction containing β-carbolines and DMT, reversed stroke-induced increases in the inflammatory markers IL-6, IL-10, and MPO activity in the prefrontal cortex and hippocampus of rats, and reduced oxidative stress markers TBARS in the prefrontal cortex and hippocampus. It also modulated mitochondrial enzyme activity in the hippocampus and cortex. However, ayahuasca did not improve neurological deficits, locomotion, anxiety-like behavior, or recognition memory. These molecular changes suggest a neuroprotective role against ischemia-induced neuroinflammation and oxidative stress, though without corresponding functional improvements in this three-day treatment study.
Behavioural Brain Research
January 5, 2025
Han Wang, Yuxuan He, Jiahao Tang et al.
5 citations
Injecting (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) into the brain's lateral ventricle of rats with PTSD-like behaviors most effectively reduces anxiety and fear when given during the reconsolidation phase of fear memory—the period after a memory is recalled and before it is stored again. The drug restored levels of three proteins in the hippocampus (GluA1, VGF, and BDNF) that were lowered by stress and fear conditioning. No significant improvements occurred when the drug was given during the acquisition or extinction phases. The findings suggest that (2R,6R)-HNK works through the VGF/BDNF/GluA1 signaling pathway in the hippocampus to alleviate PTSD-like symptoms specifically during memory reconsolidation.
Behavioural Brain Research
January 5, 2025
Santiago Castro-Zaballa, Joaquín González, Matías Cavelli et al.
4 citations
In cats, high-frequency oscillations (HFO, >100 Hz) in the brain's electrical activity are linked to breathing during wakefulness but not during sleep. A sub-anesthetic dose of ketamine increases the power of these HFO, and they remain tied to the inhalation phase of respiration. The enhanced HFO appear to originate in the olfactory bulb and travel to the prefrontal cortex. Blocking the nostrils reduces the ketamine-enhanced HFO in both regions. Auditory stimulation does not affect these oscillations. The findings suggest that ketamine's enhancement of respiration-coupled HFO may disrupt cortical information processing, potentially contributing to its neuropsychiatric effects.
Behavioural Brain Research
March 28, 2025
Teresa Belem Mares-Barbosa, Ares Orlando Cuellar-Santoyo, Victor Manuel Ruiz-Rodríguez et al.
3 citations
Repeated low-dose ketamine given for 14 days impaired nest-building and novel object recognition only in adult mice, not in young mice. In the hippocampus, gene expression of GluN1, P2X4, and P2X7 remained unchanged, while GluA2 and P2X1 increased only in young mice. Protein levels showed opposite patterns: young mice had lower P2X1 and higher P2X7, while adult mice had higher P2X1 and lower P2X7. These results suggest adult mice are more vulnerable to repeated ketamine, and differential P2X1 and P2X7 responses may contribute to behavioral changes.