Pharmacology, biochemistry, and behavior - The Consciousness Library

Network dysregulation in depression: A synthesis of HPA Axis, BDNF signaling, and neurotransmitter interactions across multidimensional systems.

Pharmacology, biochemistry, and behavior August 1, 2026 Mengyang He, Zhifei Shi, Ruijie Zhan et al.

Depression is a complex mental disorder threatening global public health. Its pathophysiological mechanisms involve multidimensional dysfunctions including the emotional-cognitive circuit, Hypothalamic-Pituitary-Adrenal (HPA) axis, neurotransmitter systems and neuroplasticity. Current studies mostly analyze each system in isolation, lacking a unified integrated framework. This review proposes...

DOI: 10.1016/j.pbb.2026.174215 Full text Major depressive disorder Neuroplasticity Bdnf/creb signaling pathway Emotional–cognitive circuit +3

The functional role of ERK activity in esketamine's antidepressant effects.

Pharmacology, biochemistry, and behavior July 26, 2026 Peng Zhang, Mengyu Wu, Keke Zhang et al.

Esketamine has been approved for the treatment of treatment-resistant depression. However, there is an unmet clinical need to extend the duration of esketamine's action to reduce the high recurrence rate after drug withdrawal and the potential side effects of repeated esketamine use. Here, we found that increasing extracellular signal-regulated kinase (ERK) activity by pharmacologically...

DOI: 10.1016/j.pbb.2026.174248 Full text Esketamine Treatment-resistant depression Bdnf-trkb signaling pathway Erk activity +1

Chronic psilocin microdosing produces limited behavioral effects and does not enhance neurogenesis in rats.

Pharmacology, biochemistry, and behavior June 30, 2026 Lucie Ladislavová, Viera Kútna, Kristýna Mazochová et al.

Psilocin (4-hydroxy-N, N-dimethyltryptamine) is a substituted tryptamine alkaloid and a nonselective serotonergic agonist acting predominantly at 5-HT2A/C receptors, with substantial binding to 5-HT1A and 5-HT2B receptors. Microdosing is the practice of taking a very small, sub-perceptual dose, typically 5% to 10% of a full recreational dose, to improve mood, creativity, and focus without...

DOI: 10.1016/j.pbb.2026.174231 Full text Anxiety Depression Behavioral testing Hippocampal neurogenesis +3

Inhibition of compulsive behavior by dextromethorphan on schedule-induced polydipsia in rats: Role of NMDA, sigma-1, and 5-HT receptors.

Pharmacology, biochemistry, and behavior May 29, 2026 Madeline T Van Fossen, Alexia G Dalton, Adam J Prus

Dextromethorphan (DM) is an FDA-approved treatment for major depressive disorder when combined with bupropion. DM functions as an inhibitor for 5-HT membrane transporters and antagonist for sigma-1 receptors (S1Rs) and NMDA receptors, which are pharmacological actions potentially therapeutically relevant for obsessive-compulsive disorder (OCD). The present study examined DM and compounds...

DOI: 10.1016/j.pbb.2026.174218 Full text Serotonin Dextromethorphan Nmda receptors Obsessive-compulsive disorder +3

Eutylone history selectively impacts the rewarding and aversive effects of cocaine, MDMA, and eutylone in female Sprague-Dawley rats.

Pharmacology, biochemistry, and behavior March 1, 2026 Negar G Ardabili, Shira Tan, María Elisa Márquez De Prado Arrarás et al.

Both the rewarding and aversive effects of a drug contribute to its abuse potential. One factor known to impact the balance of these effects is concurrent and serial polydrug use. A drug class for which such interactions are common is synthetic cathinones. In prior work, history with the synthetic cathinone eutylone had no effect on cocaine- or MDMA-induced taste avoidance in male rats,...

DOI: 10.1016/j.pbb.2026.174152 Full text MDMA Aversion Cocaine Eutylone +4

The 3,4-methylenedioxymethamphetamine (MDMA) reduces prosocial behavior in the social preference test in male and female rats.

Pharmacology, biochemistry, and behavior February 1, 2026 Daniel A Palacios-Lagunas, Juan C Hernández-mondragón, Kjell Fuxé et al. 1 citation

The promotion of prosocial behavior is a remarkable MDMA property. Such an effect is rather uncommon among other psychoactive substances and has been proposed to be of relevance for the potential therapeutic utility of MDMA. We aim to expand our knowledge of the prosocial effects of MDMA, considering sex and housing conditions as extra variables. To this end, housed individually or...

DOI: 10.1016/j.pbb.2025.174135 Full text

A systematic review of ketamine's anxiolytic potential in rodent behavioral models of anxiety and PTSD.

Pharmacology, biochemistry, and behavior February 2026 Alena Lemeshova, Kaya A Patel, Alexander J Bloom et al.

Ketamine, a nonselective NMDA-receptor antagonist, is an emerging therapeutic for treatment-resistant depression and could also be a promising treatment for anxiety and post-traumatic stress disorders. However, preclinical studies in these areas lack methodological standardization, limiting clinical translatability. This review evaluates ketamine's anxiolytic potential in rodents by examining...

DOI: 10.1016/j.pbb.2025.174144 Full text

The therapeutic use of psychedelic drugs: Legal, policy, and neuroscientific perspectives.

Pharmacology, biochemistry, and behavior November 1, 2025 Shadan Rahmani, Rachel Crupi, Anthony L Riley et al.

After many years of stigma and neglect, there is a resurgence of interest in the therapeutic use of psychedelic drugs. Anecdotal and evidence-based reports indicate psychedelics as a possible treatment for depression, anxiety, PTSD, substance abuse, and other disorders resistant to conventional medical interventions. The available data, however, are limited and the use of psychedelic substances...

DOI: 10.1016/j.pbb.2025.174087 Full text Psilocybin Drug law Drug policy Medical ethics +1

Lifelong dietary Omega-3, -6, and -9 ratios shape adult behavior and response to adolescent THC exposure in rats.

Pharmacology, biochemistry, and behavior November 2025 Ariel Frajerman, Aude Marzo, Boris Chaumette et al.

Alterations in membrane lipids are well established in schizophrenia, and diet could be an accessible, modifiable etiological factor. We examined the influence of Polyunsaturated fatty acids (PUFAs) intake throughout the lifespan on behaviour in adult rats. We further explored a possible interaction with adolescent exposure to delta-9-tetrahydrocannabinol (THC), the lipidic psychoactive...

DOI: 10.1016/j.pbb.2025.174086 Full text Brain maturation Cannabinoids Omega-3 Omega-6 +2

Advancements in psychedelic research: Effects, mechanisms, and therapeutic potential as emerging antidepressants.

Pharmacology, biochemistry, and behavior November 1, 2025 Xian-Qiang Zhang, De-Nong Liu, Qing-Shan Miao et al.

Major depressive disorder (MDD) causes great physical and mental suffering to patients while also imposing a tremendous economic burden on the global economy. Psychedelics, also known as serotonergic hallucinogens, are potent psychoactive compounds known for their ability to alter mood, perception, and a range of cognitive functions. Increasing evidence suggests that some psychedelics...

DOI: 10.1016/j.pbb.2025.174099 Full text Major depressive disorder 5-hydroxytryptamine Antidepressant effect Psychedelics

Pre-exposure to eutylone attenuates its own aversive effects but has no impact on cocaine or MDMA: A possible role of eutylone's hybrid pharmacology.

Pharmacology, biochemistry, and behavior July 1, 2025 Negar G Ardabili, Shira Tan, Anthony L Riley 1 citation

Previous research has reported that pre-exposure to a variety of drugs of abuse can impact (reduce) the aversive effects of themselves and other abused compounds, often as a function of their shared pharmacological activity. In this context, the present series of studies investigated the effects of history with the synthetic cathinone eutylone on the aversive effects of cocaine, MDMA, and...

DOI: 10.1016/j.pbb.2025.174013 Full text MDMA Cocaine Conditioned taste avoidance Drug pre-exposure +8

Emerging medications and pharmacological treatment approaches for substance use disorders.

Pharmacology, biochemistry, and behavior March 1, 2025 Joel S Raymond, Alexander G Athanasopoulos, Connie J Badolato et al. 7 citations

Medications to treat substance use disorders (SUDs) remain suboptimal or, in the case of stimulants and cannabis, non-existent. Many factors have contributed to this paucity, including the biological complexity of addiction, regulatory challenges, and a historical lack of enthusiasm among pharmaceutical companies to commit resources to this disease space. Despite these headwinds, the recent...

DOI: 10.1016/j.pbb.2024.173952 Full text

Esketamine-mediated alleviation of electroconvulsive shock-induced memory impairment is associated with the regulation of mGluR5 in depressive-like rats.

Pharmacology, biochemistry, and behavior March 1, 2025 Yiwei Shen, Wei Ran, Dawei Liu et al. 2 citations

Electroconvulsive therapy (ECT) is recognized as one of the most efficacious interventions for depression. However, it is associated with impairments in learning and memory functions. Ketamine has demonstrated potential in mitigating cognitive deficits. Notably, the metabotropic glutamate system is hypothesized to play a pivotal role in cognitive process regulation. Nevertheless, the...

DOI: 10.1016/j.pbb.2025.173955 Full text Spravato Electroconvulsive shock Learning Metabotropic glutamate receptor +7

Desvenlafaxine with mindfulness-based cognitive therapy reduces Hamilton anxiety scores compared to escitalopram with mindfulness-based cognitive therapy in treatment-resistant generalized anxiety disorder.

Pharmacology, biochemistry, and behavior March 1, 2025 Karthik Sankar, Sandhiya Ramesh, Natarajan Shanmugasundaram et al.

This study aims to assess the effectiveness of low-dose Escitalopram (10 mg) or low-dose Desvenlafaxine (25 mg) combined with mindfulness-based cognitive therapy (MBCT) in addressing challenges in treating generalized anxiety disorder (GAD), particularly in patients resistant to conventional therapies. A prospective cohort study was conducted with individuals diagnosed with treatment-resistant...

DOI: 10.1016/j.pbb.2025.173959 Full text Mindfulness Cognitive therapy Inclusive treatment Mental health +2

5-HT1B receptor activation produces rapid antidepressant-like effects in rodents.

Pharmacology, biochemistry, and behavior February 1, 2025 Erin A Clark, Lien Wang, Taleen Hanania et al. 5 citations

Ketamine is noted for its rapid onset antidepressant response and effectiveness in patients with treatment resistant depression. While most research has focused on glutamatergic mechanisms, recent studies show that antidepressant-like effects in rodents are dependent upon the serotonergic (5-HT) system and suggest a potential contribution of the 5-HT1B receptor. In this study we utilized...

DOI: 10.1016/j.pbb.2024.173917 Full text Synaptic plasticity 5-ht1b receptor agonist Lateral habenula circuit Rapid onset +5

Ketamine impairs the performance of male mice in novel recognition object test and reduces the immunoreactivity of GAD67 in the hippocampus: Role of pioglitazone.

Pharmacology, biochemistry, and behavior February 1, 2025 Talita Rodrigues, Getulio Nicola Bressan, Patrícia Zorzi Juliani et al.

Schizophrenia is a mental disorder characterized by positive, negative, and cognitive symptoms which is treated with antipsychotics. However, these drugs present several side effects and, some schizophrenia symptoms, like cognitive, are difficult to treat. The peroxisome proliferator-activated receptors-gamma (PPAR-γ) are expressed in dopaminergic neurons of the midbrain participating in the...

DOI: 10.1016/j.pbb.2024.173950 Full text Animal behavior Monoamine oxidase Open field Social interaction +6

Ketamine modulates the exploratory dynamics and homebase-related behaviors of adult zebrafish.

Pharmacology, biochemistry, and behavior December 1, 2024 Camilla W Pretzel, João V Borba, Cássio M Resmim et al. 5 citations

Anxiety can be a protective emotion when animals face aversive conditions, but is commonly associated with various neuropsychiatric disorders when pathologically exacerbated. Drug repurposing has emerged as a valuable strategy based on utilizing the existing pharmaceuticals for new therapeutic purposes. Ketamine, traditionally used as an anesthetic, acts as a non-competitive antagonist of the...

DOI: 10.1016/j.pbb.2024.173892 Full text Nmda receptor Open field test Spatio-temporal exploration Stereotyped behavior +6

Mescaline-induced behavioral alterations are mediated by 5-HT2A and 5-HT2C receptors in rats.

Pharmacology, biochemistry, and behavior December 1, 2024 Lucie Olejníková-Ladislavová, Michaela Fujáková-Lipski, Klára Šíchová et al. 5 citations

Mescaline is a classical psychedelic compound with a phenylethylamine structure that primarily acts on serotonin 5-HT2A/C receptors, but also binds to 5-HT1A and 5-HT2B receptors. Despite being the first psychedelic ever isolated and synthesized, the precise role of different serotonin receptor subtypes in its behavioral pharmacology is not fully understood. In this study, we aimed to...

DOI: 10.1016/j.pbb.2024.173903 Full text Mescaline Psychedelics hallucinogens Locomotor activity Sensorimotor gating +6

Splenic γδ T cells mediate antidepressant and prophylactic actions of arketamine in lipopolysaccharide-induced depression in mice.

Pharmacology, biochemistry, and behavior December 1, 2024 Guilin Liu, Li Ma, Akemi Sakamoto et al. 4 citations

Arketamine, the (R)-enantiomer of ketamine, exhibits both therapeutic and sustained prophylactic effects in an inflammation-driven model of depression, although the precise mechanisms remain elusive. Given the involvement of γδ T cells in inflammatory processes, this study explored their role in the effects of arketamine. To assess therapeutic outcomes, mice received lipopolysaccharide (LPS:1.0...

DOI: 10.1016/j.pbb.2024.173906 Full text Arketamine Prophylactic Spleen Antidepressants antidepressant medication +8

(2R,6R)-hydroxynorketamine alleviates PTSD-like endophenotypes by regulating the PI3K/AKT signaling pathway in rats.

Pharmacology, biochemistry, and behavior December 1, 2024 Lifen Liu, Rui Li, Lanxia Wu et al. 3 citations

Patients diagnosed with post-traumatic stress disorder (PTSD) mainly exhibit enduring adverse emotions, heightening susceptibility to suicidal thoughts and behaviors. Notably, metabolites of ketamine, particularly (2R,6R)-hydroxyketamine (HNK), have demonstrated favorable antidepressant properties. However, the precise mechanism through which HNK exerts its therapeutic effects on negative...

DOI: 10.1016/j.pbb.2024.173891 Full text Post-traumatic stress disorder 2r,6r-hnk Negative emotions Pi3k/akt signaling pathway +4

Molecular signature underlying (R)-ketamine rapid antidepressant response on anhedonic-like behavior induced by sustained exposure to stress.

Pharmacology, biochemistry, and behavior December 1, 2024 Ellen Scotton, Paola Rampelotto Ziani, Renata Luiza Boff Wilges et al. 1 citation

Anhedonia induced by sustained stress exposure is a hallmark symptom of major depressive disorder (MDD) and in rodents, it can be accessed through the sucrose preference test (SPT). (R)-ketamine is a fast-acting antidepressant with less detrimental side effects and abuse liability compared to racemic ketamine. The present study combined high-throughput proteomics and network analysis to...

DOI: 10.1016/j.pbb.2024.173882 Full text Major depressive disorder R-ketamine treatment response Anhedonic-like behavior Molecular targets +6

Vaporized Δ9-tetrahydrocannabinol exposure in utero has negative effects on attention in a dose- and sex-dependent manner.

Pharmacology, biochemistry, and behavior September 1, 2024 Samantha L Penman, Nicole M Roeder, Jia Wang et al. 9 citations

There has been an increasing use of cannabis during pregnancy in recent years. Studies have indicated that THC exposure in utero may increase the risk of attention deficits and memory impairments in adolescence. The goal of the present study is to investigate the effects of vaporized THC exposure during pregnancy on offspring memory and attention performance in early and late adolescence....

DOI: 10.1016/j.pbb.2024.173808 Full text THC Attention Cognition Memory +2

Environmental enrichment enhances the antidepressant effect of ketamine and ameliorates spatial memory deficits in adult rats.

Pharmacology, biochemistry, and behavior July 1, 2024 Deren Aykan, Mert Genc, Gunes Unal 8 citations

Ketamine is a rapid-acting antidepressant associated with various cognitive side effects. To mitigate these side effects while enhancing efficacy, it can be co-administered with other antidepressants. In our study, we adopted a similar strategy by combining ketamine with environmental enrichment, a potent sensory-motor paradigm, in adult male Wistar rats. We divided the animals into four groups...

DOI: 10.1016/j.pbb.2024.173790 Full text Behavioral despair C-fos Environmental enrichment Habenula +5

A role of gut-brain axis on prophylactic actions of arketamine in male mice exposed to chronic restrain stress.

Pharmacology, biochemistry, and behavior May 1, 2024 Li Ma, Akifumi Eguchi, Guilin Liu et al. 11 citations

The gut-brain axis, which includes gut microbiota and microbiome-derived metabolites, might be implicated in depression. We reported the sustained prophylactic effects of a new antidepressant arketamine in chronic restrain stress (CRS) model of depression. In this study, we investigated the role of gut-brain axis on the prophylactic effects of arketamine in the CRS (7 days) model. Pretreatment...

DOI: 10.1016/j.pbb.2024.173736 Full text Chronic restrain stress Gut microbiota Metabolites Prophylactic effect: resilience +5

Established sensitization of ethanol-induced locomotor activity is not reversed by psilocybin or the 5-HT2A receptor agonist TCB-2 in male DBA/2J mice.

Pharmacology, biochemistry, and behavior February 1, 2024 Paul J Fletcher, Zhaoxia Li, Xiao Dong Ji et al. 2 citations

Psychedelic drugs, which share in common 5-HT2A receptor agonist activity, have shown promise in treating alcohol-use disorders (AUDs). Repeated exposure to ethanol (EtOH) induces molecular and behavioural changes reflective of neuroadaptations that may contribute to addiction. Psychedelic drugs can induce neuroplasticity also, raising the possibility that their potential clinical effects in...

DOI: 10.1016/j.pbb.2023.173703 Full text Psilocybin Ethanol Locomotor activity Sensitization +6

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