Behavioural Brain Research
June 25, 2023
Rodolpho Pereira de Oliveira, Thaís S. 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
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.
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.
Behavioural Brain Research
July 1, 2026
L. Rosenfeld, Rebecca L. Silton, Erica K Yuen
This review examines how mindfulness meditation produces health benefits through changes in attention processes and associated brain networks, particularly the executive control network and default mode network. It presents evidence of durable neuroplasticity linked to beneficial psychological outcomes. Electroencephalography (EEG) methods are highlighted as necessary for investigating the rapid dynamics of adaptive attention processes altered by meditation. The review discusses how malleable attention networks influence adaptive attention processes, leading to reduced psychological distress and improved emotional wellbeing. It emphasizes an interdisciplinary perspective bridging neurocognitive methodologies with clinical outcomes to build future evidence-based mindfulness strategies.
Behavioural Brain Research
August 1, 2025
C. Romein, Mika Mautner-Rohde, Karis Colyer-Patel et al.
Long-term cannabis use may alter brain responses to social situations, increasing neural sensitivity to social influence while decreasing sensitivity to social exclusion, stress, and reward, according to a systematic review of 8 studies on social cognition. Findings from 21 studies on emotion recognition are inconsistent, with some showing increased and others decreased activity in the amygdala, cingulate cortex, and frontal areas in cannabis users compared to controls. The authors caution that results are preliminary due to few studies per area and methodological differences. Causal relationships and the roles of user characteristics like symptom severity, gender, and age remain unclear.
Behavioural Brain Research
February 1, 2024
L. M. Melo, W. A. de Barros, Â. de Fátima et al.
The psychedelic substance 25H-NBOMe disrupts maternal behavior in lactating rats, impairing nest-building and pup retrieval, without affecting body weight of mothers or pups. Offspring of exposed mothers show reduced social play behavior. Higher doses cause more pronounced maternal disruptions, while lower doses, which do not visibly alter maternal behavior, still reduce offspring social play, suggesting direct effects of the drug. The findings highlight risks of using 25H-NBOMe during lactation, emphasizing its detrimental impact on maternal care and offspring neurodevelopment.
Behavioural Brain Research
July 1, 2022
Li-Min Zhang, Na Liu, Lucy Cao et al.
Pregnant mice given high-dose S-ketamine (60 mg/kg) all miscarried after the first injection. Low- and medium-dose S-ketamine (15 and 30 mg/kg) administered from gestational day 14 to 18 led to ADHD-like behaviors (increased open-arm time, reduced freezing in fear conditioning) and, at the medium dose, depression-like behaviors (reduced locomotion, increased immobility) in offspring. Changes in astrocytic activation, synaptic dysfunction, and decreased inhibitory presynaptic proteins were observed in the hippocampus, amygdala, and habenula nucleus. The authors conclude that S-ketamine may cause detrimental effects on developing brains and call for further study.
Behavioural Brain Research
June 1, 2022
C. Pennartz
Conscious experience is a multimodal, situational survey—a best-guess representation of body and environment built by the brain. Five hallmarks characterize it: multimodal richness, situatedness, unity, dynamics, and intentionality. Consciousness serves a biological function, enabling goal-directed, planned behavior rather than reflexes or habits. Predictive processing models help explain the neural mechanisms, but the Hard Problem—why such activity yields phenomenal experience—remains. The author proposes that multi-level representations emergently give rise to spatially wide superinferences corresponding to experience. Neurorepresentationalism is compared with other neural theories, and its implications for assessing consciousness in animals, AI, and unresponsive patients are discussed.
Behavioural Brain Research
February 23, 2022
V. Occhieppo, O. Basmadjian, N. A. Marchese et al.
Blocking the AT1 receptor with candesartan prevented long-lasting schizophrenia-like behavioral changes and altered neuronal activation patterns caused by repeated ketamine administration in adult male rats. These effects involved the GABAergic system and parvalbumin-expressing interneurons in several brain regions. However, AT1 receptors were not involved in the acute psychotomimetic effects of a single ketamine dose. The findings suggest AT1 receptors play a key role in enduring alterations induced by repeated psychostimulant exposure and in the development of psychiatric conditions.
Behavioural Brain Research
February 15, 2022
Vassiliy Tsytsarev
Two approaches to defining consciousness exist: one treats qualia as inaccessible to third-person science, tying it to the 'hard problem' of why subjective experience arises from physical changes; the other imposes no a priori limits, including first-person experience as an empirical subject. Historically, biology distinguishes proximate from ultimate causation, but this may be insufficient for studying consciousness-brain interaction. Current neuroscience assumes consciousness emerges from neural networks, particularly cortical and thalamocortical circuits, linking directly to clinical research on disorders of consciousness. This review generalizes and systematizes accumulated experimental data in this area.
Behavioural Brain Research
February 15, 2022
Armin Zlomuzica, Ekrem Dere
Brain pathologies and mental diseases impair conscious cognition and behavior, but valid animal models of consciousness for preclinical research are lacking. The platform theory proposes that the brain enters a conscious operation mode when mental representations are actively maintained and manipulated in working memory. Using this theory as a framework, behavioral paradigms are categorized by the level of consciousness involved. A consciousness behavioral test battery for rodents is proposed, including tests of working memory, episodic-like memory, prospective memory, detour tests, and operant conditioning with concurrent schedules. Performance on these tests can be contrasted with tasks requiring lower consciousness levels. A second comprehensive battery controls for non-conscious behavioral phenotypes. This framework may guide deciphering the neurobiological basis of consciousness.
Behavioural Brain Research
December 1, 2021
W. Wiese, K. Friston
Artificial intelligence methods used in computational psychiatry raise ethical issues including fairness, data ownership, and privacy. Beyond these, AI applications may transform how we conceive of autonomy and privacy, and computational psychiatry may change how mental disorders are categorized and classified. Since many mental disorders involve disturbed conscious experiences, successful computational psychiatry applications could improve understanding of such disorders. However, even successful applications may fail to account for all aspects of disordered conscious experiences. The authors discuss both prospects and pitfalls of these transformative effects.
Behavioural Brain Research
November 1, 2021
Haiyang Liu, Ke-Hui Hu, Yingjie Peng et al.
During dexmedetomidine-induced sedation, the brain's functional networks become more fragmented and dynamic, with increased switching rates and decreased integration compared to wakefulness; these changes largely reverse upon recovery of consciousness. The study tracked dynamic network reconfiguration using fMRI data from 21 healthy subjects and multilayer network analysis, comparing wakefulness, sedation, and recovery states. The findings suggest that altered states of consciousness involve a whole-brain pattern of higher modular dynamics and more fragmented communication, offering insights into the neural basis of consciousness and potential clinical relevance for disorders of consciousness.
Behavioural Brain Research
October 1, 2020
Lukas Lenhart, Ruth Steiger, Michaela Waibel et al.
Short-term focused attention meditation training (averaging 7.3 weeks) in 27 healthy, meditation-naïve adults induced dynamic brain changes, including gray matter increases in the insula, caudate nucleus, and frontal cortices, and decreases in parietotemporal regions, the right medial prefrontal cortex, and the parahippocampal gyrus. Fractional anisotropy increased in the right hippocampus, basal ganglia, and adjacent regions. Some alterations correlated with reduced state anxiety. The results suggest that even brief meditation training can produce broad cortical reorganization and altered axonal integrity, with patterns differing from prior studies.
Behavioural Brain Research
August 17, 2020
Meryem Grabski, Anna Borissova, Beth Marsh et al.
Ketamine's acute psychoactive effects may not be consistently linked to its antidepressant efficacy. A systematic review of 21 studies involving 891 patients with psychiatric diagnoses (mostly treatment-resistant depression) found that 26% of 41 assessed associations between acute effects and treatment outcomes were significant. Dissociation, most commonly measured by the CADSS, was not reliably associated with antidepressant outcomes. The evidence is too limited to draw definite conclusions, and the field would benefit from more rigorous methodology and broader assessment tools.
Behavioural Brain Research
February 13, 2020
S. Kokane, Ross J. Armant, Carlos A. Bolaños-Guzmán et al.
Ketamine shows rapid antidepressant effects in major depressive disorder, suicidal tendencies, and treatment-resistant depression, but these effects are transient and require repeated clinic visits. Repeated exposure raises concern because ketamine has abuse liability, and depression and addiction share overlapping neural circuitry and molecular mechanisms. The review outlines limited knowledge of ketamine's neurobiological underpinnings mediating antidepressant effects and correlates them to its abuse potential. Although speculative, repeated ketamine use for depression could lead to substance use disorder, warranting caution. The lack of understanding of long-term effects and mechanisms is a limiting factor that needs systematic investigation before repeated use in depressed patients.
Behavioural Brain Research
November 6, 2019
Mei-Dan Wei, Yuhong Wang, Kun Lu et al.
Ketamine rapidly reduces depressive-like behaviors and facilitates the extinction of fear memories in adolescent mice, an effect linked to presynaptic mechanisms that restore long-term potentiation. The findings suggest a potential new treatment strategy for post-traumatic stress disorder, which affects about eight percent of the population and is characterized by impaired fear memory extinction.
Behavioural Brain Research
September 2, 2019
M L Shawn Bates, Keith A Trujillo
Repeated ketamine use during adolescence produces greater acute locomotor stimulation than in adulthood, but long-lasting behavioral sensitization—a marker of addiction-related neuroadaptation—persists only when exposure occurs in adults. In rats, 10 daily injections of 25 mg/kg ketamine caused immediate locomotor sensitization in both age groups, yet after 20 days of abstinence only adults retained this effect. No cross-sensitization to dextromethorphan was observed. Ketamine did not cause statistically significant cognitive deficits in spatial learning or object recognition in either age group, though adult-treated animals showed a trend toward spatial learning impairments. The findings suggest that adolescent and adult brains respond differently to repeated ketamine, with lasting neuroadaptations in adults that may contribute to addiction risk.
Behavioural Brain Research
August 1, 2019
Zhongwei Xiong, Yuko Fujita, Kai Zhang et al.
(R)-ketamine, but not its final metabolite (2R,6R)-hydroxynorketamine (HNK), produced rapid and sustained antidepressant effects in mice susceptible to chronic social defeat stress. It also improved elevated plasma levels of the inflammatory bone marker RANKL, restored the reduced OPG/RANKL ratio, and attenuated decreased bone mineral density in these mice. These findings suggest (R)-ketamine may have beneficial effects on both depression-like behavior and bone abnormalities in susceptible mice, indicating it could be a potential therapeutic drug for bone metabolism problems in depressed patients.
Behavioural Brain Research
May 17, 2019
Mohaddeseh Ebrahimi-Ghiri, Mohammad Nasehi, Mohammad-Reza Zarrindast
Combining low, ineffective doses of the cannabinoid CB1 receptor agonist ACPA and the β-carboline harmaline produced both anxiolytic- and antidepressant-like effects in male NMRI mice, whereas either compound alone at higher doses caused anxiogenic-like responses. ACPA at 1 mg/kg reduced open-arm activity in the elevated plus maze and decreased immobility in the forced swim test, indicating anxiogenic and antidepressant effects, respectively. β-carbolines such as harmane, norharmane, and harmaline also induced anxiogenic behavior at certain doses, with some doses showing antidepressant-like effects. Only the combination of subthreshold ACPA (0.5 mg/kg) and harmaline (1.25 mg/kg) yielded beneficial behavioral changes and reduced locomotion, suggesting a potential therapeutic strategy for anxiety and depression.
Behavioural Brain Research
May 1, 2019
Wei Wang, Le Liu, Xiu Yang et al.
Mice that showed a rise in plasma corticosterone two hours after a single social defeat stress went on to develop depressive-like behaviors after ten days of repeated defeat. Resilient mice did not show this early corticosterone increase. Susceptible mice maintained elevated corticosterone even 48 hours after the last stress. Giving corticosterone in drinking water made mice susceptible. The glucocorticoid receptor antagonist mifepristone reduced susceptibility. A single dose of ketamine improved depressive-like behaviors, lowered corticosterone, and restored glucocorticoid receptor expression and nuclear translocation in the hippocampus. Abnormal corticosterone after stress may predict susceptibility to depression, and ketamine may work by normalizing HPA axis response.
Behavioural Brain Research
January 15, 2018
Hilary A Marusak, Farrah Elrahal, Craig A Peters et al.
In children and adolescents aged 6-17, trait mindfulness is linked to dynamic, time-varying patterns of brain connectivity rather than to static connectivity. More mindful youth transitioned more frequently between different brain states, spent less time in a particular connectivity state, and showed reduced connectivity between salience/emotion and central executive networks in one state. The number of state transitions mediated the link between higher mindfulness and lower anxiety, suggesting a neural mechanism for mindfulness benefits on psychological health in youth.