Briana K. Chen

Brain-derived neurotrophic factor (BDNF) exon VI promoter is implicated in mediating activity-induced synthesis of hippocampal BDNF. BDNF is implicated in (R,S)-ketamine’s antidepressant effects, but its role in (R,S)-ketamine-mediated prophylaxis is unknown. Using BDNF-e6 mice, in which promoter VI-driven BDNF production is disrupted, we tested its necessity for (R,S)-ketamine’s prophylactic effects.

Social media provides journals with valuable opportunities to communicate with scholars and the public, and rapidly disseminate new publications. In recent years, the Neuropsychopharmacology (NPP) social media team created multiple initiatives on X (formerly Twitter) to highlight the journal’s publications and activities. We examined whether these initiatives promoted readership and identified effective posting strategies for engaging NPP’s audience by analyzing analytics from the @npp_journal X account (i.e., total engagement, URL clicks) and article accesses reported by NPP’s publisher, Springer Nature. In 2023–2024, we found that article promotions at the time of publication produced the most engagement compared to other initiatives on X; these promotions coincided with increased web traffic to articles. Posts that included an author’s X handle received more engagement compared to untagged posts, which also corresponded with an increase in article accesses. The number of URL clicks on articles featured in This Week in NPP (TWiNPP), a weekly summary of new publications launched in 2023, increased after it was rescheduled from Fridays to Tuesdays following observations that posts made earlier in the week received the most engagement. The number of accesses to articles featured in TWiNPP did not differ compared to articles published before the rollout of TWiNPP; however, this endeavor may still provide benefit given the recent reported declines in X usage. These findings support the use of X to promote NPP publications and maximize research visibility. These findings also suggest the journal may benefit from diversifying its online presence to other popular platforms to broaden engagement of its readership.

Serotonin (5-HT) receptors and N-methyl-D-aspartate receptors (NMDARs) have both been implicated in stress-induced psychiatric disorders. However, there is a paucity of studies evaluating the effectiveness of novel combinatorial pharmacological treatments to treat stress-related disorders. Here, we evaluated whether administration of combinatorial (R,S)-ketamine, an NMDAR antagonist and Food and Drug Administration (FDA)-approved anesthetic, and prucalopride, a 5-HT type IV receptor (5-HT₄R) agonist and FDA-approved drug for chronic idiopathic constipation (CIC), would have additional effects when administered after stress. A single injection of saline (Sal), (R,S)-ketamine (K), prucalopride (P), or a combined dose of (R,S)-ketamine and prucalopride (K + P) was administered for 1x, 2x, or 7x per week for 2 weeks after either contextual fear conditioning (CFC), learned helplessness (LH), stress enhanced fear learning (SEFL), or chronic corticosterone (CORT) stress in both sexes. Drug efficacy was assayed using assays to measure fear, behavioral despair, perseverative, and/or hyponeophagia. Combinatorial drug administration was also tested using intranasal delivery. We found that combinatorial K + P exerted additional effects, compared to either drug alone, in reducing a variety of stress-induced behaviors in both sexes. Moreover, intranasal dosing was also effective. Our results indicate that chronic administration of K + P has extended benefits for combating stress-induced pathophysiology. Our findings provide strong evidence that future clinical studies using this chronic treatment strategy may prove advantageous in decreasing a broad range of stress-induced psychiatric disorders.

Neuropsychopharmacology (NPP) offers the option to publish articles in different tiers of an open access (OA) publishing system: Green, Bronze, or Hybrid. Green articles follow a standard access (SA) subscription model, in which readers must pay a subscription fee to access article content on the publisher’s website. Bronze articles are selected at the publisher’s discretion and offer free availability to readers at the same article processing charge (APC) as Green articles. Hybrid articles are fully OA, but authors pay an increased APC to ensure public access. Here, we aimed to determine whether publishing tier affect the impact and reach of scientific articles in NPP. A sample of 6000 articles published between 2001–2021 were chosen for the analysis. Articles were separated by article type and publication year. Citation counts and Altmetric scores were compared between the three tiers. Bronze articles received significantly more citations than Green and Hybrid articles overall. However, when analyzed by year, Bronze and Hybrid articles received comparable citation counts within the past decade. Altmetric scores were comparable between all tiers, although this effect varied by year. Our findings indicate that free availability of article content on the publisher’s website is associated with an increase in citations of NPP articles but may only provide a moderate boost in Altmetric score. Overall, our results suggest that easily accessible article content is most often cited by readers, but that the higher APCs of Hybrid tier publishing may not guarantee increased scholarly or social impact.

BACKGROUND: Serotonin (5-HT) receptors and N -methyl-D-aspartate receptors (NMDARs) have both been implicated in the pathophysiology of depression and anxiety disorders. Here, we evaluated whether targeting both receptors through combined dosing of ( R , S )-ketamine, an NMDAR antagonist, and prucalopride, a serotonin type IV receptor (5-HT ₄ R) agonist, would have additive effects, resulting in reductions in stress-induced fear, behavioral despair, and hyponeophagia. METHODS: A single injection of saline (Sal), ( R , S )-ketamine (K), prucalopride (P), or a combined dose of ( R , S )-ketamine and prucalopride (K+P) was administered before or after contextual fear conditioning (CFC) stress in both sexes. Drug efficacy was assayed using the forced swim test (FST), elevated plus maze (EPM), open field (OF), marble burying (MB), and novelty-suppressed feeding (NSF). Patch clamp electrophysiology was used to measure the effects of combined drug on neural activity in hippocampal CA3. c-fos and parvalbumin (PV) expression in the hippocampus (HPC) and medial prefrontal cortex (mPFC) was examined using immunohistochemistry and network analysis. RESULTS: We found that a combination of K+P, given before or after stress, exerted additive effects, compared to either drug alone, in reducing a variety of stress-induced behaviors in both sexes. Combined K+P administration significantly altered c-fos and PV expression and network activity in the HPC and mPFC. CONCLUSIONS: Our results indicate that combined K+P has additive benefits for combating stress-induced pathophysiology, both at the behavioral and neural level. Our findings provide preliminary evidence that future clinical studies using this combined treatment strategy may prove advantageous in protecting against a broader range of stress-induced psychiatric disorders.

INTRODUCTION: Traumatic brain injury (TBI) is a debilitating neurological disorder caused by an impact to the head by an outside force. TBI results in persistent cognitive impairments, including fear generalization, the inability to distinguish between aversive and neutral stimuli. The mechanisms underlying fear generalization have not been fully elucidated, and there are no targeted therapeutics to alleviate this symptom of TBI. METHODS: To identify the neural ensembles mediating fear generalization, we utilized the ArcCreER ^T2 x enhanced yellow fluorescent protein (EYFP) mice, which allow for activity-dependent labeling and quantification of memory traces. Mice were administered a sham surgery or the controlled cortical impact (CCI) model of TBI. Mice were then administered a contextual fear discrimination (CFD) paradigm and memory traces were quantified in numerous brain regions. In a separate group of mice, we tested if ( R,S )-ketamine could decrease fear generalization and alter the corresponding memory traces in TBI mice. RESULTS: TBI mice exhibited increased fear generalization when compared with sham mice. This behavioral phenotype was paralleled by altered memory traces in the DG, CA3, and amygdala, but not by alterations in inflammation or sleep. In TBI mice, ( R,S )-ketamine facilitated fear discrimination and this behavioral improvement was reflected in DG memory trace activity. CONCLUSIONS: These data show that TBI induces fear generalization by altering fear memory traces, and that this deficit can be improved with a single injection of ( R,S )-ketamine. This work enhances our understanding of the neural basis of TBI-induced fear generalization and reveals potential therapeutic avenues for alleviating this symptom.