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
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
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 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
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
July 14, 2017
Allan V Kalueff, Aleksandra Kaluyeva, Emeline 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
January 5, 2025
Khanyiso Bright Shangase, Mluleki Luvuno, Musa 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.
Behavioural brain research
June 25, 2023
Rodolpho Pereira de Oliveira, Thais Yokoyama, Lucas de Santana Cardoso Thomaz et al.
2 citations
Activation of 5-HT2A receptors in the inferior colliculus (IC) by the agonist DOI reduces prepulse inhibition (PPI) of the acoustic startle in male Wistar rats, mimicking a schizophrenia-like deficit. A neural pathway connecting the IC and the pedunculopontine tegmental nucleus (PPTg) was identified. DOI injection decreased c-Fos-labeled cells in both the IC and PPTg, suggesting increased GABA activity. Blocking GABAA receptors in the PPTg with bicuculline prevented the PPI deficit caused by DOI in the IC. These findings indicate that IC 5-HT2A receptors help regulate inhibitory pathways mediating PPI, involving GABAergic transmission in the IC-PPTg circuit.
Behavioural brain research
June 27, 2025
Carlos M Contreras, Ana G Gutiérrez-García
1 citation
A 15-minute forced swim session in male Wistar rats altered the responsiveness of connections between the hippocampal CA3 region and the medial prefrontal cortex (mPFC). Ketamine, given 60 minutes after the stressor, reduced immobility in a later swim test without affecting general locomotion. In the mPFC, CA3 stimulation normally inhibited the prelimbic region and excited the infralimbic region; ketamine reversed the infralimbic response to inhibition. Prior stress amplified the inhibitory response in the infralimbic region, an effect that ketamine abolished. The prelimbic region's response was sensitive to stress but not to ketamine, whereas the infralimbic region's response was sensitive to ketamine only when stress had occurred.
Behavioural brain research
July 9, 2026
Jeffrey R Kelly, Lindsey S Brasfield, Aryssa H Kelsey et al.
Hydroxynorketamine isomers have stereospecific and context-dependent effects on anxiety-like behavior and stress-induced hyperarousal in zebrafish. Under baseline conditions, (2R,6R)-hydroxynorketamine (RANK) produced a robust anxiolytic-like profile, reducing bottom-dwelling and erratic movements, whereas (2S,6S)-hydroxynorketamine (SHANK) increased anxiety-like behavior, shown by more bottom-dwelling and longer latency to ascend. Hydrocortisone exposure induced a hyperarousal phenotype with increased locomotion and erratic movements but no change in classical anxiety measures. Pretreatment with either RANK or SHANK attenuated this hyperarousal, restoring behavior toward control levels, but only RANK produced consistent anxiolytic-like effects across conditions.
Behavioural brain research
March 28, 2026
Lucas Villar Pedrosa Da Silva Pantoja, Luiza Fernanda Ramos Soares, Brenda Costa Da Conceição et al.
Adolescent female rats that received intranasal ketamine for three consecutive days, mimicking weekend recreational use, showed impairments in episodic, social, and working memory 24 hours after the last dose. The memory deficits were accompanied by reduced serotonin and norepinephrine levels in the hippocampus and prefrontal cortex. The findings indicate that early ketamine withdrawal following acute exposure disrupts cognition and monoamine signaling in the adolescent female brain.
Behavioural brain research
April 12, 2025
Eamonn Eeles, Dana Pourzinal, Jalal Baland et al.
Consciousness can be divided into access consciousness (A-C), which involves reasoning and memory and is measurable, and phenomenal consciousness (P-C), the subjective experience of 'what it's like,' which is harder to test directly. Researchers previously developed indirect measures of P-C using subjective questions informed by objective dimensions of A-C. To bridge the gap before clinical validation, they adapted a thought experiment from quantum physics—'Schrödinger's cat and mouse'—to test the principles underlying their operationalization of P-C. This thought experiment suggests their theories on consciousness, particularly P-C, resonate with disorders of consciousness such as delirium.