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cotinine, memory

Lisa J Germeroth, Matthew J Carpenter, Nathaniel L Baker, Brett Froeliger, Steven D LaRowe, Michael E Saladin
Importance: Recent research on addiction-related memory processes suggests that protracted extinction training following brief cue-elicited memory retrieval (ie, retrieval-extinction [R-E] training) can attenuate/eradicate the ability of cues to elicit learned behaviors. One study reported that cue-elicited craving among detoxified heroin addicts was substantially attenuated following R-E training and through 6-month follow-up. Objective: To build on these impressive findings by examining whether R-E training could attenuate smoking-related craving and behavior...
March 1, 2017: JAMA Psychiatry
Marta Pardo, Eleonore Beurel, Richard S Jope
Cotinine is the major metabolite of nicotine and has displayed some capacity for improving cognition in mouse models following chronic administration. We tested if acute cotinine treatment is capable of improving cognition in the mouse model of Fragile X syndrome, Fmr1(-/-) knockout mice, and if this is related to inhibition by cotinine treatment of glycogen synthase kinase-3β (GSK3β), which is abnormally active in Fmr1(-/-) mice. Acute cotinine treatment increased the inhibitory serine-phosphorylation of GSK3β and the activating phosphorylation of AKT, which can mediate serine-phosphorylation of GSK3β, in both wild-type and Fmr1(-/-) mouse hippocampus...
February 2017: European Journal of Neuroscience
Alexandre Iarkov, Doreen Appunn, Valentina Echeverria
PURPOSE: Most cancer patients treated with systemic adjuvant chemotherapy endure long-lasting side effects including decrease in concentration, forgetfulness and slower thinking, which are globally termed "chemobrain." Cotinine, the main derivative of nicotine, improved visual and spatial working memory and decreased depressive-like behavior in an animal model of chemotherapy-induced cognitive impairment. METHODS: In this study, we investigated the effect of cotinine on weight gain, locomotor activity, cognitive abilities and depressive-like behavior in rats treated with the chemotherapy mix, cyclophosphamide, methotrexate and 5-fluorouracil...
October 5, 2016: Cancer Chemotherapy and Pharmacology
Natasha E Wright, Judith A Strong, Erika R Gilbart, Skyler G Shollenbarger, Krista M Lisdahl
OBJECTIVE: Ecstasy use is associated with memory deficits. Serotonin transporter gene (5-HTTLPR) polymorphisms have been linked with memory function in healthy samples. The present pilot study investigated the influence of 5-HTTLPR polymorphisms on memory performance in ecstasy users, marijuana-using controls, and non-drug-using controls, after a minimum of 7 days of abstinence. METHOD: Data were collected from 116 young adults (18-25 years-old), including 45 controls, 42 marijuana users, and 29 ecstasy users, and were balanced for 5-HTTLPR genotype...
2015: PloS One
George E Barreto, Alexander Yarkov, Marcos Avila-Rodriguez, Gjumrakch Aliev, Valentina Echeverria
Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after experiencing trauma. Actual therapies do not help majority of patients with PTSD. Moreover, extinguished fear memories usually reappear in the individuals when exposed to trauma cues. New drugs to reduce the impact of conditioned cues in eliciting abnormal fear responses are urgently required. Cotinine, the main metabolite of nicotine, decreased anxiety and depressive-like behavior, and enhanced fear extinction in mouse models of PTSD...
2015: Current Pharmaceutical Design
L Ponzoni, M Moretti, M Sala, F Fasoli, V Mucchietto, V Lucini, G Cannazza, G Gallesi, C N Castellana, F Clementi, M Zoli, C Gotti, D Braida
Nicotine is the primary addictive substance in tobacco smoke and electronic cigarette (e-cig) vapour. Methodological limitations have made it difficult to compare the role of the nicotine and non-nicotine constituents of tobacco smoke. The aim of this study was to compare the effects of traditional cigarette smoke and e-cig vapour containing the same amount of nicotine in male BALB/c mice exposed to the smoke of 21 cigarettes or e-cig vapour containing 16.8 mg of nicotine delivered by means of a mechanical ventilator for three 30-min sessions/day for seven weeks...
October 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
George E Barreto, Alexander Iarkov, Valentina Echeverria Moran
Parkinson's disease (PD) is a progressive neurodegenerative disorder, which is characterized by neuroinflammation, dopaminergic neuronal cell death and motor dysfunction, and for which there are no proven effective treatments. The negative correlation between tobacco consumption and PD suggests that tobacco-derived compounds can be beneficial against PD. Nicotine, the more studied alkaloid derived from tobacco, is considered to be responsible for the beneficial behavioral and neurological effects of tobacco use in PD...
2014: Frontiers in Aging Neuroscience
Alvin V Terry, Patrick M Callahan, Daniel Bertrand
The nicotine metabolite cotinine (1-methyl-5-[3-pyridynl]-2-pyrrolidinone), like its precursor, has been found to exhibit procognitive and neuroprotective effects in some model systems; however, the mechanism of these effects is unknown. In this study, both the R-(+) and S-(-) isomers of cotinine were initially evaluated in an extensive profiling screen and found to be relatively inactive across a wide range of potential pharmacologic targets. Electrophysiological studies on human α4β2 and α7 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes confirmed the absence of agonistic activity of cotinine at α4β2 or α7 nAChRs...
February 2015: Journal of Pharmacology and Experimental Therapeutics
James Loughead, E Paul Wileyto, Kosha Ruparel, Mary Falcone, Ryan Hopson, Ruben Gur, Caryn Lerman
Brief abstinence from smoking impairs cognition, particularly executive function, and this has a role in relapse to smoking. This study examined whether working memory-related brain activity predicts subsequent smoking relapse above and beyond standard clinical and behavioral measures. Eighty treatment-seeking smokers completed two functional magnetic resonance imaging sessions (smoking satiety vs 24 h abstinence challenge) during performance of a visual N-back task. Brief counseling and a short-term quit attempt followed...
May 2015: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Sagar Patel, J Alex Grizzell, Rosalee Holmes, Ross Zeitlin, Rosalynn Solomon, Thomas L Sutton, Adeeb Rohani, Laura C Charry, Alexandre Iarkov, Takashi Mori, Valentina Echeverria Moran
Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-β (Aβ) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development...
2014: Frontiers in Aging Neuroscience
J Alex Grizzell, Valentina Echeverria
Tobacco consumption is far higher among a number of psychiatric and neurological diseases, supporting the notion that some component(s) of tobacco may underlie the oft-reported reduction in associated symptoms during tobacco use. Popular dogma holds that this component is nicotine. However, increasing evidence support theories that cotinine, the main metabolite of nicotine, may underlie at least some of nicotine's actions in the nervous system, apart from its adverse cardiovascular and habit forming effects...
October 2015: Neurochemical Research
J Alex Grizzell, Alexandre Iarkov, Rosalee Holmes, Takahashi Mori, Valentina Echeverria
Chronic stress underlies and/or exacerbates many psychiatric conditions and often results in memory impairment as well as depressive symptoms. Such afflicted individuals use tobacco more than the general population and this has been suggested as a form of self-medication. Cotinine, the predominant metabolite of nicotine, may underlie such behavior as it has been shown to ameliorate anxiety and memory loss in animal models. In this study, we sought to investigate the effects of cotinine on working memory and depressive-like behavior in mice subjected to prolonged restraint...
July 15, 2014: Behavioural Brain Research
Kristin M Wildeboer-Andrud, Lijun Zheng, Kevin S Choo, Karen E Stevens
Cotinine, a major metabolite of nicotine, has produced improved learning and memory in rodents and non-human primates and corrects apomorphine-induced loss of pre-pulse startle inhibition in rats. The present study assessed cotinine, both acute and chronic (7-day), in the sensory inhibition paradigm in DBA/2 mice. These mice spontaneously show a deficit in hippocampal sensory inhibition, as assessed by the P20-N40 EEG paradigm, which models the deficit observed in schizophrenia patients. Anesthetized DBA/2 mice were recorded in the CA3 region of hippocampus for inhibition of paired, identical auditory stimuli, then administered cotinine (0...
February 2014: Pharmacology, Biochemistry, and Behavior
Peter Kochunov, Xiaoming Du, Lauren V Moran, Hemalatha Sampath, S Andrea Wijtenburg, Yihong Yang, Laura M Rowland, Elliot A Stein, L Elliot Hong
INTRODUCTION: Nicotinic acetylcholine receptors are present in the cerebral white matter (WM). We hypothesized that WM response to nicotine can be detected by diffusion tensor imaging (DTI); and that such responses may be associated with nicotine-led cognitive enhancement in sustained attention. METHODS: A randomized, nicotine-placebo patch, crossover, double-blind clinical trial in two non-overlapping cohorts of smokers was used to test the hypothesis. The discovery cohort consisted of 39 subjects (N = 20/19 controls/schizophrenic patients, age = 36...
2013: Frontiers in Pharmacology
R B de Aguiar, G M Parfitt, J Jaboinski, D M Barros
The present work evaluated the effects of nicotine (NIC), cotinine (COT), mecamylamine (MEC), methyllycaconitine (MLA) and dihydro-beta-eritroidine (DHβE) on memory extinction and the following biochemical parameters of the hippocampus: lipid peroxidation (LPO), antioxidant capacity (AC) and the phosphorylation of Extracellular-Signal-Regulated Kinase (ERK 1/2). Young male rats that were implanted bilaterally with cannulae were submitted to memory extinction tests sessions, and their hippocampi were dissected for biochemical assays...
August 2013: Neuropharmacology
Karen J Hartwell, Todd Lematty, Aimee L McRae-Clark, Kevin M Gray, Mark S George, Kathleen T Brady
BACKGROUND: Varenicline has been shown to reduce cigarette craving during a quit attempt. OBJECTIVES: Use BOLD fMRI to explore differences in smoking cue reactivity at baseline and after five weeks of varenicline smoking cessation treatment. METHODS: Treatment-seeking nicotine-dependent adult smokers underwent BOLD fMRI scans with block presentation of visual smoking, neutral, and rest cues under two conditions: craving or resisting the urge to smoke at baseline and following 5 weeks of standard varenicline therapy...
March 2013: American Journal of Drug and Alcohol Abuse
Wajiha Z Akhtar, Elena M Andresen, Michael B Cannell, Xiaohui Xu
UNLABELLED: Background Studies show that active smoking may be associated with cognitive decline. However, the consequence of secondhand smoke on cognitive and physical performance remains unclear. The purpose of this study was to assess the association of secondhand smoke with cognitive performance and physical function using a population-based sample. METHODS: Data of 2,542 non-smoking participants from the 1999-2002 National Health and Nutrition Examination Survey were analyzed...
February 2013: Environmental Research
Valentina Echeverria Moran
A greater incidence of tobacco consumption occurs among individuals with psychiatric conditions including post-traumatic stress disorder (PTSD), bipolar disorder, major depression, and schizophrenia, compared with the general population. Even when still controversial, it has been postulated that smoking is a form of self-medication that reduces psychiatric symptoms among individuals with these disorders. To better understand the component(s) of tobacco-inducing smoking behavior, greater attention has been directed toward nicotine...
2012: Frontiers in Pharmacology
Anton L Beer, Devavrat Vartak, Mark W Greenlee
Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices. The cholinergic system is known to modulate declarative learning. In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation. However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning. Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT)...
January 2013: Neuropharmacology
Valentina Echeverria, Ross Zeitlin
Tobacco smoking has been correlated with a lower incidence of Alzheimer's disease (AD). This negative correlation has been attributed to nicotine's properties. However, the undesired side-effects of nicotine and the absence of clear evidence of positive effects of this drug on the cognitive abilities of AD patients have decreased the enthusiasm for its therapeutic use. In this review, we discuss evidence showing that cotinine, the main metabolite of nicotine, has many of the beneficial effects but none of the negative side-effects of its precursor...
July 2012: CNS Neuroscience & Therapeutics
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