scholarly journals Nicotine Self-administration Is Not Increased in the Methylazoxymethanol Acetate Rodent Model of Schizophrenia

2019 ◽  
Vol 22 (2) ◽  
pp. 204-212 ◽  
Author(s):  
Jillian J Weeks ◽  
Laura E Rupprecht ◽  
Anthony A Grace ◽  
Eric C Donny ◽  
Alan F Sved

Abstract Introduction Patients with schizophrenia (SCZ) smoke at a rate of 4–5 times higher than the general population, contributing to negative health consequences in this group. One possible explanation for this increased smoking is that individuals with SCZ find nicotine (NIC) more reinforcing. However, data supporting this possibility are limited. Methods The present experiments examined self-administration of NIC, alone or in combination with other reinforcers, across a range of doses in the methylazoxymethanol acetate (MAM) rodent model of SCZ. Results MAM and control animals did not differ in NIC self-administration across a range of doses and schedules of reinforcement, in both standard 1-hour self-administration sessions and 23-hour extended access sessions. However, MAM animals responded less for sucrose or reinforcing visual stimuli alone or when paired with NIC. Conclusions To the extent that MAM-treated rats are a valid model of SCZ, these results suggest that increased NIC reinforcement does not account for increased smoking in SCZ patients. Implications This study is the first to utilize nicotine self-administration, the gold standard for studying nicotine reinforcement, in the methylazoxymethanol acetate model of schizophrenia, which is arguably the most comprehensive animal model of the disease currently available. Our assessment found no evidence of increased nicotine reinforcement in methylazoxymethanol acetate animals, suggesting that increased reinforcement may not perpetuate increased smoking in schizophrenia patients.

Author(s):  
Aaron Lawson ◽  
Marie Vaganay-Miller ◽  
Robert Cameron

Every year, thousands of people from the UK travel to other countries for work and leisure. Europe, and particularly Spain, is one of the most popular travel destinations for people from the UK. However, it is known that travel to other countries can enhance the risk of communicable disease transmission from person to person, especially when a new one emerges. Adequate hand hygiene behaviour and compliance is widely accepted as being a simple, effective method in preventing the spread of communicable diseases that may be contracted during travel abroad. There is a well-established body of work investigating hand hygiene practice and compliance in community settings, but no recent studies have examined the hand hygiene practice and compliance of the general population when travelling abroad or in a cross-European context. The findings of this study indicated that most UK members of the general population when travelling abroad have a good level of understanding of the importance of adequate hand hygiene practice and compliance and its role regarding communicable disease prevention and control. As such, self-reported levels of compliance were high. Similar findings were made for Spanish members of the general population. However, while self-reported perceptions of adequacy of hand hygiene performance were relatively high, particularly among UK respondents, this was not supported by responses specifically focused on hand hygiene behaviour. However, differences in self-reported adequacy regarding the importance of handwashing versus hand drying, the number of steps that should be followed and the length of time that should be spent washing and drying hands were found for each group. This suggests that self-reported compliance may reflect intention to practice hand hygiene rather than true compliance. It also suggests that there are gaps in knowledge regarding the adequate method of hand hygiene among the cohort as a whole, and indeed these differences may account be a factor in for the high transmission rates of communicable disease when travelling abroad.


Biostatistics ◽  
2021 ◽  
Author(s):  
Lingjiao Zhang ◽  
Yanyuan Ma ◽  
Daniel Herman ◽  
Jinbo Chen

Summary Validation of phenotyping models using Electronic Health Records (EHRs) data conventionally requires gold-standard case and control labels. The labeling process requires clinical experts to retrospectively review patients’ medical charts, therefore is labor intensive and time consuming. For some disease conditions, it is prohibitive to identify the gold-standard controls because routine clinical assessments are performed for selective patients who are deemed to possibly have the condition. To build a model for phenotyping patients in EHRs, the most readily accessible data are often for a cohort consisting of a set of gold-standard cases and a large number of unlabeled patients. Hereby, we propose methods for assessing model calibration and discrimination using such “positive-only” EHR data that does not require gold-standard controls, provided that the labeled cases are representative of all cases. For model calibration, we propose a novel statistic that aggregates differences between model-free and model-based estimated numbers of cases across risk subgroups, which asymptotically follows a Chi-squared distribution. We additionally demonstrate that the calibration slope can also be estimated using such “positive-only” data. We propose consistent estimators for discrimination measures and derive their large sample properties. We demonstrate performances of the proposed methods through extensive simulation studies and apply them to Penn Medicine EHRs to validate two preliminary models for predicting the risk of primary aldosteronism.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akhil Sharma ◽  
Arman Harutyunyan ◽  
Bernard L. Schneider ◽  
Anna Moszczynska

AbstractThere is no FDA-approved medication for methamphetamine (METH) use disorder. New therapeutic approaches are needed, especially for people who use METH heavily and are at high risk for overdose. This study used genetically engineered rats to evaluate PARKIN as a potential target for METH use disorder. PARKIN knockout, PARKIN-overexpressing, and wild-type young adult male Long Evans rats were trained to self-administer high doses of METH using an extended-access METH self-administration paradigm. Reinforcing/rewarding properties of METH were assessed by quantifying drug-taking behavior and time spent in a METH-paired environment. PARKIN knockout rats self-administered more METH and spent more time in the METH-paired environment than wild-type rats. Wild-type rats overexpressing PARKIN self-administered less METH and spent less time in the METH-paired environment. PARKIN knockout rats overexpressing PARKIN self-administered less METH during the first half of drug self-administration days than PARKIN-deficient rats. The results indicate that rats with PARKIN excess or PARKIN deficit are useful models for studying neural substrates underlying “resilience” or vulnerability to METH use disorder and identify PARKIN as a novel potential drug target to treat heavy use of METH.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Francis Sahngun Nahm ◽  
Zee-Yong Park ◽  
Sang-Soep Nahm ◽  
Yong Chul Kim ◽  
Pyung Bok Lee

Background. Complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder. Although the exact pathophysiology of CRPS is not fully understood, central and peripheral mechanisms might be involved in the development of this disorder. To reveal the central mechanism of CRPS, we conducted a proteomic analysis of rat cerebrum using the chronic postischemia pain (CPIP) model, a novel experimental model of CRPS.Materials and Methods. After generating the CPIP animal model, we performed a proteomic analysis of the rat cerebrum using a multidimensional protein identification technology, and screened the proteins differentially expressed between the CPIP and control groups.Results. A total of 155 proteins were differentially expressed between the CPIP and control groups: 125 increased and 30 decreased; expressions of proteins related to cell signaling, synaptic plasticity, regulation of cell proliferation, and cytoskeletal formation were increased in the CPIP group. However, proenkephalin A, cereblon, and neuroserpin were decreased in CPIP group.Conclusion. Altered expression of cerebral proteins in the CPIP model indicates cerebral involvement in the pathogenesis of CRPS. Further study is required to elucidate the roles of these proteins in the development and maintenance of CRPS.


2004 ◽  
Vol 11 (3) ◽  
pp. 563-568 ◽  
Author(s):  
Roma Kalra ◽  
Shashi P. Singh ◽  
Juan C. Pena-Philippides ◽  
Raymond J. Langley ◽  
Seddigheh Razani-Boroujerdi ◽  
...  

ABSTRACT To study the immunological effects of nicotine, there are several rodent models for chronic nicotine administration. These models include subcutaneously implanted miniosmotic pumps, nicotine-spiked drinking water, and self-administration via jugular cannulae. Administration of nicotine via these routes affects the immune system. Smokers frequently use nicotine patches to quit smoking, and the immunological effects of nicotine patches are largely unknown. To determine whether the nicotine patch affects the immune system, nicotine patches were affixed daily onto the backs of Lewis rats for 3 to 4 weeks. The patches efficiently raised the levels of nicotine and cotinine in serum and strongly inhibited the antibody-forming cell response of spleen cells to sheep red blood cells. The nicotine patch also suppressed the concanavalin A-induced T-cell proliferation and mobilization of intracellular Ca2+ by spleen cells, as well as the fever response of animals to subcutaneous administration of turpentine. Moreover, immunosuppression was associated with chronic activation of protein tyrosine kinase and phospholipase C-γ1 activities. Thus, in this animal model of nicotine administration, the nicotine patch efficiently raises the levels of nicotine and cotinine in serum and impairs both the immune and inflammatory responses.


Author(s):  
Thomas Guiho ◽  
Christine Azevedo Coste ◽  
Claire Delleci ◽  
Jean-Patrick Chenu ◽  
Jean-Rodolphe Vignes ◽  
...  

Spinal cord injuries (SCI) result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self-) catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session.


1992 ◽  
Vol 73 (1) ◽  
pp. 340-345 ◽  
Author(s):  
D. S. Jardine ◽  
R. H. Haschke

A mathematical model of heat balance in human infants suggests that it may be possible for severe hyperthermia to develop if an infant is unable to remove his blankets in response to overheating (thermal entrapment). This hypothesis was tested in an animal model of weanling piglets. Ten piglets were warmed in a radiant heater to rectal temperature of 41 degrees C to simulate a fever. Animals in the experimental and control groups were removed from the heater and covered with ordinary infant blankets (to a thickness of approximately 3 cm). Endogenously produced heat caused the animals to warm to 42 degrees C. At this point, the control animals were uncovered. They rapidly cooled to normal body temperature. Animals in the experimental group remained covered until they expired from hyperthermia at 43.9 +/- 0.7 degrees C (SD) after 96 +/- 43 (SD) min. These data show that lethal hyperthermia may result from thermal entrapment. This finding may help clarify the role that hyperthermia may play in illnesses such as hemorrhagic shock and encephalopathy syndrome and some cases of sudden infant death syndrome.


2011 ◽  
Vol 17 (2) ◽  
pp. 300-308 ◽  
Author(s):  
Eric P. Zorrilla ◽  
Sunmee Wee ◽  
Yu Zhao ◽  
Sheila Specio ◽  
Benjamin Boutrel ◽  
...  

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