Translational Aspects of the Novel Object Recognition Task in Rats Abstinent Following Sub-Chronic Treatment with Phencyclidine (PCP): Effects of Modafinil and Relevance to Cognitive Deficits in Schizophrenia

Phencyclidine (PCP) induces a behavioral syndrome in rodents that bears remarkable similarities to some of the core symptoms observed in schizophrenic patients, among those cognitive deficits. The successful alleviation of cognitive impairments associated with schizophrenia (CIAS) has become a major focus of research efforts as they remain largely untreated. The aim of the present study was to investigate the effects of selected antipsychotic and cognition enhancing drugs, namely haloperidol, risperidone, donepezil, and modafinil in an animal model widely used in preclinical schizophrenia research. To this end, the novel object recognition (NOR) task was applied to rats abstinent following sub-chronic treatment with PCP. Rats were administered either PCP (5 mg/kg, i.p.) or vehicle twice a day for 7 days, followed by a 7-day washout period, before testing in NOR. Upon testing, vehicle-treated rats successfully discriminated between novel and familiar objects, an effect abolished in rats that had previously been exposed to PCP treatment. Acute treatment with modafinil (64 mg/kg, p.o.) ameliorated the PCP-induced deficit in novel object exploration, whereas haloperidol (0.1 mg/kg, s.c.), risperidone (0.2 mg/kg, i.p.), and donepezil (3 mg/kg, p.o.) were without significant effect. Given the negligible efficacy of haloperidol and risperidone, and the contradictory data with donepezil to treat CIAS in the clinic, together with the promising preliminary pro-cognitive effects of modafinil in certain subsets of schizophrenic patients, the sub-chronic PCP–NOR abstinence paradigm may represent an attractive option for the identification of potential novel treatments for CIAS

Comparison of 25‐hydroxyvitamin D concentration in chimpanzee dried blood spots and serum

BackgroundDried blood spots (DBS) are used in human medicine to measure total 25‐hydroxyvitamin D (25‐OHD) in the blood. However, this easy and affordable sampling technique has not been evaluated in primates to measure vitamin D concentrations.ObjectivesWe aimed to compare 25‐OHD measurements in chimpanzee serum at two different laboratories and determine the precision and accuracy of the DBS method by comparing DBS and serum results.MethodsBlood samples from 17 captive chimpanzees were collected, and 25‐OHD3 and 25‐OHD2 were measured in serum at two accredited laboratories using liquid chromatography‐tandem mass spectrometry. The same analytes were measured on DBS cards, and results were compared with that of serum. Data were assessed using the Spearman correlation, Deming regression, and Bland‐Altman analyses. ResultsThe correlation coefficient between the two measurements in serum was r s = .51 (P = .04), and the mean bias was −1.25 ± 14.83. When comparing 25‐OHD concentrations measured in DBS and serum at the same laboratory, the r s was 0.7 (P = .002), and the mean bias was 1.42 ± 14.58. Estimated intra‐assay and inter‐assay coefficients of variation for DBS results were 6% and 12.6%, respectively. ConclusionsAlthough substantial analytical variability was found in 25‐OHD measurements regardless of the sample type, the identification of both constant and proportional error and wider limits of agreement with the DBS technique makes the interpretation of DBS results challenging, especially for values close to clinical cut‐off points. The DBS and serum methods were not interchangeable, and further studies are needed to validate DBS samples for vitamin D measurements in chimpanzees

Unfinished: Women Filmmakers in Process (catalogue)

Unfinished: Women Filmmakers in Process is curated by Alix Beeston and Stefan Solomon. This programme emerges from Beeston and Solomon’s Incomplete: The Feminist Possibilities of the Unfinished Film, a forthcoming collection of essays by scholars and filmmakers out with the University of California Press in June 2023

Discovery of os cordis in the cardiac skeleton of chimpanzees (Pan troglodytes)

© 2020, The Author(s). Cardiovascular diseases, especially idiopathic myocardial fibrosis, is one of the most significant causes of morbidity and mortality in captive great apes. This study compared the structure and morphology of 16 hearts from chimpanzees (Pan troglodytes) which were either healthy or affected by myocardial fibrosis using X-ray microtomography. In four hearts, a single, hyperdense structure was detected within the right fibrous trigone of the cardiac skeleton. High resolution scans and histopathology revealed trabecular bones in two cases, hyaline cartilage in another case and a focus of mineralised fibro-cartilaginous metaplasia with endochondral ossification in the last case. Four other animals presented with multiple foci of ectopic calcification within the walls of the great vessels. All hearts affected by marked myocardial fibrosis presented with bone or cartilage formation, and increased collagen levels in tissues adjacent to the bone/cartilage, while unaffected hearts did not present with os cordis or cartilago cordis. The presence of an os cordis has been described in some ruminants, camelids, and otters, but never in great apes. This novel research indicates that an os cordis and cartilago cordis is present in some chimpanzees, particularly those affected by myocardial fibrosis, and could influence the risk of cardiac arrhythmias and sudden death

Is there a potential of misuse for venlafaxine and bupropion?

© 2018 Schifano and Chiappini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Objective: Traditionally, studies on the nonmedical use of pharmaceutical products have focused on controlled substances; e.g. opiates/opioids; and benzodiazepines. Although both bupropion and venlafaxine have been reported as being misused, only anecdotal reports have been made available so far. Hence, the European Monitoring Agency (EMA) Adverse Drug Reactions (ADRs), misuse/abuse/dependence and withdrawal, venlafaxine- and bupropion-related, database was here analyzed. Methods: All EMA spontaneous reports relating to venlafaxine (2005-2016) and bupropion (2003-2016) notifications were here analyzed, to provide a descriptive analysis by source, gender, age, and type of report. The UK-based, 2000-2016, Yellow Card Scheme pharmacovigilance database, bupropion and venlafaxine withdrawal reports were compared as well with those pertaining to fluoxetine and paroxetine. Results: Out of 20,720 (bupropion) and 47,516 (venlafaxine) total number of ADRs, some 2,232 (10.8%), and 4,071 (8.5%) misuse/abuse/dependence ADRs were respectively associated with bupropion and venlafaxine. Conversely, bupropion withdrawal-related ADRs were here reported in 299/20,720 (1.44%) cases and in 914/47,516 (1.92%) cases for venlafaxine. Overall, all bupropion and venlafaxine misuse-/abuse-/dependence- and withdrawal-ADRs were related to a respective number of 264 and 447 patients. According to the Proportional Reporting Ratio (PRR) computation, in comparison with venlafaxine bupropion resulted to be more frequently misused/abused (PRR: 1.50), but less frequently associated with both dependence (PRR: 0.92) and withdrawal (PRR: 0.77) issues. Yellow Card Scheme data suggested that paroxetine and venlafaxine, in comparison with fluoxetine and bupropion, were associated with higher number of withdrawal-related reports. Conclusions: The dopaminergic, stimulant-like, bupropion activities may be associated with its possible recreational value. Present data may confirm that the occurrence of a withdrawal syndrome may be a significant issue for venlafaxine-treated patients.Peer reviewedFinal Published versio

Discovery Of A Bone In Chimpanzee Hearts

The os cordis (heart bone) is a rare bone found only in a few animals in the world. We discovered an os cordis in some chimpanzees. The os cordis was found in males and females, and in young and old animals. It was not present in chimps with healthy hearts, only in those with severe heart disease. We also discovered that a tissue called cartilage was present around the bone. The presence of cartilage gives us clues about how and why these rare bones develop

CyPPA, a Positive SK3/SK2 Modulator, Reduces Activity of Dopaminergic Neurons, Inhibits Dopamine Release, and Counteracts Hyperdopaminergic Behaviors Induced by Methylphenidate1

Dopamine (DA) containing midbrain neurons play critical roles in several psychiatric and neurological diseases, including schizophrenia and attention deficit hyperactivity disorder, and the substantia nigra pars compacta neurons selectively degenerate in Parkinson’s disease. Pharmacological modulation of DA receptors and transporters are well established approaches for treatment of DA-related disorders. Direct modulation of the DA system by influencing the discharge pattern of these autonomously firing neurons has yet to be exploited as a potential therapeutic strategy. Small conductance Ca2+-activated K+ channels (SK channels), in particular the SK3 subtype, are important in the physiology of DA neurons, and agents modifying SK channel activity could potentially affect DA signaling and DA-related behaviors. Here we show that cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA), a subtype-selective positive modulator of SK channels (SK3 > SK2 > > > SK1, IK), decreased spontaneous firing rate, increased the duration of the apamin-sensitive afterhyperpolarization, and caused an activity-dependent inhibition of current-evoked action potentials in DA neurons from both mouse and rat midbrain slices. Using an immunocytochemically and pharmacologically validated DA release assay employing cultured DA neurons from rats, we show that CyPPA repressed DA release in a concentration-dependent manner with a maximal effect equal to the D2 receptor agonist quinpirole. In vivo studies revealed that systemic administration of CyPPA attenuated methylphenidate-induced hyperactivity and stereotypic behaviors in mice. Taken together, the data accentuate the important role played by SK3 channels in the physiology of DA neurons, and indicate that their facilitation by CyPPA profoundly influences physiological as well as pharmacologically induced hyperdopaminergic behavior

Idiopathic myocardial fibrosis in captive chimpanzees (Pan troglodytes)

Cardiovascular disorders and, predominantly idiopathic myocardial fibrosis, are frequently associated with mortality among zoo-housed chimpanzees (Pan troglodytes). Formalin-fixed whole hearts of deceased chimpanzees housed in zoos (n=33) or in an African sanctuary (n=2) underwent detailed macroscopic and histopathologic examination using a standardized protocol. Archived histological slides from the hearts of 23 additional African sanctuary-housed chimpanzees were also examined. Myocardial fibrosis (MF) was identified in 30/33 (91%) of the zoo-housed chimpanzees but none of the 25 sanctuary-housed chimpanzees MF was shown to be characterized by both interstitial and replacement fibrosis. Immunophenotyping demonstrated that these fibrotic lesions were accompanied by the increased presence of macrophages, alpha smooth muscle actin-positive myofibroblasts and a minimal to mild T-cell dominant infiltration. There was no convincing evidence of cardiotropic viral infection, or suggestion that diabetes mellitus or vitamin E or selenium deficiency are associated with the presence of the lesion. However, serum vitamin D concentrations among zoo-housed chimpanzees were found to be lower in seasons of low UV light levels

Selective serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors use and risk of fractures in adults: a systematic review and meta-analysis

Objective: to evaluate the association between SSRI and SNRI use and risk of fractures in older adults. Methods: We systematically identified and analyzed observational studies comparing SSRI/SNRI use for depression with non-SSRI/SNRI use with a primary outcome of risk of fractures in older adults. We searched for studies in MEDLINE, PsycINFO, EMBASE, DARE, the Cochrane Library, Web of Science clinical trials research registers from 2011 for SSRIs and 1990 for SNRIs to November 29, 2016. Results: Thirty-three studies met our inclusion criteria, 23 studies were included in meta-analysis: 9 case-control studies and 14 cohort studies. A 1.67-fold increase in the risk of fracture for SSRI users compared to non-users was observed (Relative Risk 1.67, 95% CI 1.56-1.79, p=0.000). The risk of fracture increases with their long-term use: within 1 year the risk is 2.9% or one additional fracture in every 85 users; within 5 years the risk is 13.4% or one additional fracture in every 19 users. In meta-regression we found that the increase in risk did not differ across age groups (OR=1.006; p=0.173). A limited number of studies on SNRIs use and the risk of fractures prevented us from conducting a meta-analysis. Conclusions: Our systematic review showed an association between risk of fracture and the use of SSRIs, especially with increasing use. Age does not increase this risk. No such conclusions can be drawn about the effect of SNRIs on the risk of fracture due to a lack of studies