Emerging human laboratory and preclinical drug self-administration data suggest that a history of contingent abused drug exposure impairs performance in operant discrimination procedures, such as delayed nonmatching-to-sample (DNMTS), that are hypothesized to assess components of executive function. However, these preclinical discrimination studies have exclusively used food as the reinforcer and the effects of drugs as reinforcers in these operant procedures are unknown. The present study determined effects of contingent intravenous remifentanil injections on DNMTS performance hypothesized to assess 1 aspect of executive function, working memory. Daily behavioral sessions consisted of 2 components with sequential intravenous remifentanil (0, 0.01-1.0 μg/kg/injection) or food (0, 1-10 pellets) availability in nonopioid dependent male rhesus monkeys (n = 3). Remifentanil functioned as a reinforcer in the DNMTS procedure. Similar delay-dependent DNMTS accuracy was observed under both remifentanil- and food-maintained components, such that higher accuracies were maintained at shorter (0.1-1.0 s) delays and lower accuracies approaching chance performance were maintained at longer (10-32 s) delays. Remifentanil maintained significantly lower initial DNMTS accuracy compared to food. Reinforcer magnitude was not an important determinant of DNMTS accuracy for either remifentanil or food. These results extend the range of experimental procedures under which drugs function as reinforcers. Furthermore, the selective remifentanil-induced decrease in initial DNMTS accuracy is consistent with a selective impairment of attentional, but not memorial, processes. (PsycINFO Database Record
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http://dx.doi.org/10.1037/pha0000154 | DOI Listing |
Nucleic Acids Res
July 2023
Institute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
The specificity of DNMT1 for hemimethylated DNA is a central feature for the inheritance of DNA methylation. We investigated this property in competitive methylation kinetics using hemimethylated (HM), hemihydroxymethylated (OH) and unmethylated (UM) substrates with single CpG sites in a randomized sequence context. DNMT1 shows a strong flanking sequence dependent HM/UM specificity of 80-fold on average, which is slightly enhanced on long hemimethylated DNA substrates.
View Article and Find Full Text PDFExp Clin Psychopharmacol
December 2017
Department of Pharmacology and Toxicology, Virginia Commonwealth University.
Emerging human laboratory and preclinical drug self-administration data suggest that a history of contingent abused drug exposure impairs performance in operant discrimination procedures, such as delayed nonmatching-to-sample (DNMTS), that are hypothesized to assess components of executive function. However, these preclinical discrimination studies have exclusively used food as the reinforcer and the effects of drugs as reinforcers in these operant procedures are unknown. The present study determined effects of contingent intravenous remifentanil injections on DNMTS performance hypothesized to assess 1 aspect of executive function, working memory.
View Article and Find Full Text PDFDiabetologia
August 2017
Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Medicine), Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan.
Aims/hypothesis: Overeating of dietary fats causes obesity in humans and rodents. Recent studies in humans and rodents have demonstrated that addiction to fats shares a common mechanism with addiction to alcohol, nicotine and narcotics in terms of a dysfunction of brain reward systems. It has been highlighted that a high-fat diet (HFD) attenuates dopamine D2 receptor (D2R) signalling in the striatum, a pivotal regulator of the brain reward system, resulting in hedonic overeating.
View Article and Find Full Text PDFOncotarget
March 2016
Surgical Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
Unlabelled: BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC.
Results: The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis.
J Mol Graph Model
July 2015
Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, 130015 Cartagena, Colombia.
DNA methyltransferase inhibitors (DNMTis) have become an alternative for cancer therapies. However, only two DNMTis have been approved as anticancer drugs, although with some restrictions. Natural products (NPs) are a promising source of drugs.
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