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  • 1
    ISSN: 1432-2072
    Keywords: Lead ; Monkeys ; Psychopharmacology ; Delayed spatial alternation ; L-dopa ; Scopolamine ; Haloperidol ; Sulpiride ; Amphetamine ; Physostigmine ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated pharmacological manipulations of the cholinergic (ACh) and dopaminergic (DA) transmitter systems in monkeys with a long-term lead-induced cognitive deficit on delayed spatial alternation (DSA). Both ACh and DA have been found to be affected by developmental lead exposure and to be involved with performance on spatial learning and memory tasks. The lead-induced deficit in performance accuracy on DSA persisted throughout the 2 years of this experiment, which ended more than 8 years after the end of the postnatal lead exposure. Acute administration of agonists and antagonists of the ACh and DA systems did not elicit differential effects from the lead-exposed and control groups in terms of DSA per cent correct performance. The ACh antagonist, scopolamine, caused a dose-related decline in performance in both groups. Significant amelioration of the lead-induced DSA deficit was achieved by chronic treatment with the DA agonist, L-dopa. After withdrawal from L-dopa, the lead-related deficit reappeared. Improvement in performance of the lead-treated group was also seen after chronic amphetamine administration, but this effect was not significant. These data implicate DA mechanisms in the long-lasting cognitive effects of developmental lead exposure. The alleviation of the deficit with chronic administration of a DA precursor points to a possible line of treatment for the cognitive effects of developmental lead exposure.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 138 (1998), S. 217-230 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Memory ; Cognition ; Attention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Nicotinic cholinergic systems are involved with several important aspects of cognitive function including attention, learning and memory. Nicotinic cholinergic receptors are located in many regions of the brain, including areas important for cognitive function such as the hippocampus and frontal cortex. Nicotinic agonists have been found in rodent and non-human primate studies to improve performance on a variety of memory tasks. In a complementary fashion, nicotinic antagonists such as mecamylamine impair working memory function. In humans, similar effects have been seen. Nicotinic agonist treatment can improve attention, learning and memory and nicotinic antagonist treatment can cause deficits. To define the neural substrates of nicotinic involvement in cognitive function, three areas of investigation are underway. 1) Critical neuroanatomic loci for nicotinic effects are beginning to be determined. The hippocampus, frontal cortex and midbrain dopaminergic nuclei have been found to be important sites of action for nicotinic involvement in memory function. 2) Nicotinic receptor subtype involvement in cognitive function is being studied. There has been considerable recent work identifying nicotinic receptor subunit conformation including alpha and beta subunits. Nicotinic receptor subtypes appear to be associated with different functional systems; however, much remains to be done to determine the precise role each subtype plays in terms of cognitive function. 3) Nicotinic interactions with other transmitter systems are being assessed. Nicotine receptors interact in important ways with other systems to affect cognitive functioning, including muscarinic ACh, dopamine, norepinepherine, serotonin, glutamate, and other systems. Nicotinic function in clinical populations and potential for therapeutics has been investigated for Alzheimer’s disease, Parkinson’s disease, schizophrenia and attention deficit/hyperactivity disorder. Areas which need to receive greater attention are the exact anatomical location and the specific receptor subtypes critically involved in nicotine’s effects. In addition, more work needs to be done to develop and determine the efficacy and safety of novel nicotinic ligands for use in the long-term treatment of human cognitive disorders.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 140 (1998), S. 135-141 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Attention ; Transdermal nicotine ; Nicotine skin patches
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nicotine has been shown to improve attentiveness in smokers and attenuate attentional deficits in Alzheimer’s disease patients, schizophrenics and adults with attention-deficit/hyperactivity disorder (ADHD). The current study was conducted to determine whether nicotine administered via transdermal patches would improve attentiveness in non-smoking adults without attentional deficits. The subjects underwent the nicotine and placebo exposure in a counterbalanced double-blind manner. Measures of treatment effect included the Profile of Mood States (POMS), Conners’ computerized Continuous Performance Test (CPT) of attentiveness and a computerized interval-timing task. The subjects were administered a 7 mg/day nicotine transdermal patch for 4.5 h during a morning session. Nicotine significantly increased self-perceived vigor as measured by the POMS test. On the CPT, nicotine significantly decreased the number of errors of omission without causing increases in either errors of commission or correct hit reaction time. Nicotine also significantly decreased the variance of hit reaction time and the composite measure of attentiveness. This study shows that, in addition to reducing attentional impairment, nicotine administered via transdermal patches can improve attentiveness in normal adult nonsmokers.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 143 (1999), S. 158-165 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Alzheimer’s disease ; Attention ; Nicotine skin patches
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Acute nicotine injections have been found to improve attentional performance in patients with Alzheimer’s disease (AD), but little is known about chronic nicotine effects. Objective: The present study was undertaken to evaluate the clinical and neuropsychological effects of chronic transdermal nicotine in Alzheimer’s disease subjects over a 4-week period. Methods: The double-blind, placebo controlled, cross-over study consisted of two 4-week periods separated by a 2-week washout period. Patients wore the nicotine patch (Nicotrol®) for 16 h a day at the following doses: 5 mg/day during week 1, 10 mg/day during weeks 2 and 3 and 5 mg/day during week 4. The eight subjects had mild to moderate AD and were otherwise healthy. Results: Nicotine significantly improved attentional performance as measured by the Conners’ continuous performance test (CPT). There was a significant reduction in errors of omission on the CPT which continued throughout the period of chronic nicotine administration. The variability of hit reaction time (reaction time for correct responses) on the CPT was also significantly reduced by chronic nicotine. Nicotine did not improve performance on other tests measuring motor and memory function. Conclusions: The sustained improvement in attention found in this study with nicotine dermal patches is encouraging. However, the lack of detected effects of nicotine treatment on other cognitive and behavioral domains in this study leaves questions concerning the clinical impact of nicotinic treatment in Alzheimer’s disease. The modest size of this study limited statistical power which may have been needed to detect more subtle but clinically significant cognitive effects. Higher doses of nicotine, other nicotinic ligands or combination treatment of nicotine with other therapies may be efficacious for producing broader therapeutic effects.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 123 (1996), S. 88-97 
    ISSN: 1432-2072
    Keywords: Nicotine ; Memory ; Rats ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acute and chronic nicotine administration has been repeatedly been found in our laboratory to improve working memory performance of normal adult rats in the radial-arm maze. The current study was conducted to determine if acute or chronic nicotine administration would improve working memory performance in aged rats. Sixteen young adult (3–7 months) and 32 aged (24–28 months) male Sprague-Dawley rats were trained on an eight-arm radial maze. A significant age-related choice deficit was seen during the 21 sessions of training. After training, half of the rats in each age group were implanted with nicotine-containing osmotic minipumps and the other half implanted with vehicle-containing pumps. Consistent with previous work, the young adult rats given chronic nicotine (approximately 5 mg/kg per day as measured as nicotine base) showed a significant improvement in working memory performance. In contrast, the aged rats did not show a significant effect of this dose of chronic nicotine. After a 2 week withdrawal period the remaining rats underwent a series of acute drug challenges with nicotinic and muscarinic agonists and antagonists as well as the dopaminergic antagonist haloperidol. Mecamylamine and haloperidol impaired the memory performance of the young adult rats, whereas the aged rats showed no effect. In contrast, scopolamine impaired performance of both young adult and aged rats in a similar manner. Both pilocarpine and nicotine improved the memory performance of the aged rats, but did not improve the young adult rats, possibly due to a ceiling effect on performance. During the cholinergic agonist drug phase, the aged rats which had previously been given chronic nicotine infusions showed better performance than those which had not. The resistance of the aged rats to chronic nicotine-induced working memory improvements and acute mecamylamine-induced working memory deficits may have resulted from the decline in nicotinic receptors seen with aging. Chronic co-administration of the nicotinic antagonist mecamylamine in a previous study was found to abolish the chronic nicotine-induced working memory improvement. The aged rats were resistant to haloperidol-induced deficits which may have resulted from the decrease in dopaminergic receptors seen with aging. Interestingly, acute cholinergic agonists including nicotine did improve working memory performance in the aged rats and previous chronic nicotine infusion was beneficial during the period of acute cholinergic agonist challenge. This suggests that nicotinic treatment may be of use for treating age associated memory impairments but that special dosing regimens may be required.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 119 (1995), S. 124-126 
    ISSN: 1432-2072
    Keywords: Schizophrenia ; Smoking ; Nicotine ; Haloperidol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ten patients with schizophrenia participated in 120-min free-smoking sessions when actively psychotic and free of antipsychotic medications, and again after the initiation of haloperidol treatment. During these free-smoking sessions they had access to cigarettes ad libitum. Their expired air carbon monoxide (CO) and plasma nicotine and cotinine levels were measured at the end of the 120-min free-smoking sessions. These patients smoked more after starting haloperidol treatment, relative to their baseline rate of smoking when free of antipsychotic medications, as evidenced by significantly higher expired CO and plasma nicotine levels.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2072
    Keywords: Nicotine ; Attention Deficit/Hyperactivity Disorder ; Attention ; Treatment ; Nicotine skin patches
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several lines of evidence suggest that nicotine may be useful in treating the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). The current study was an acute, placebo-controlled double-blind experiment to determine whether nicotine might be useful as an alternative treatment of adults with ADHD symptomatology. Six smokers and 11 nonsmokers who were outpatient referrals for ADHD were diagnosed by DSM-IV criteria. Measures of treatment effect included the Clinical Global Impressions (CGI) scale, Hopkins' symptom check list (SCL-90-R), the Profile of Mood States (POMS), Conners' computerized Continuous Performance Test (CPT), the Stroop test, and an interval-timing task. The smokers underwent overnight deprivation from smoking and were given a 21 mg/day nicotine skin patch for 4.5 h during a morning session. The nonsmokers were given a 7 mg/day nicotine skin patch for 4.5 h during a morning session. Active and placebo patches were given in a counterbalanced order approximately 1 week apart. Nicotine caused a significant overall nicotine-induced improvement on the CGI. This effect was significant when only the nonsmokers were considered, which indicated that it was not due merely to withdrawal relief. Nicotine caused significantly increased vigor as measured by the POMS test. Nicotine caused an overall significant reduction in reaction time (RT) on the CPT, as well as, with the smokers, a significant reduction in another index of inattention, variability in reaction time over trial blocks. Nicotine improved accuracy of time estimation and lowered variability of time-estimation response curves. Because improvements occurred among nonsmokers, the nicotine effect appears not to be merely a relief of withdrawal symptoms. It is concluded that nicotine deserves further clincal trials with ADHD.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Chemistry and technology of fuels and oils 18 (1982), S. 423-425 
    ISSN: 1573-8310
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Chemistry of natural compounds 1 (1966), S. 160-164 
    ISSN: 1573-8388
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary 1. A comparative study of pig pepsin and the proteolytic enzyme which accompanies it (gelatinase) has been carried out. 2. As shown by paper electrophoresis, gelatinase is a less acidic protein than pepsin. 3. Like pepsin, gelatinase ruptures peptide bonds in hemoglobin, gelatin, and some dipeptides. A special feature of gelatinase is its well-defined capacity for reducing the viscosity of gelatin solutions. The possible causes of the specific nature of the action of gelatinase on gelatin have been considered.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Chemistry of natural compounds 10 (1975), S. 231-233 
    ISSN: 1573-8388
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Conclusions A system of buffers for the separation of acid proteinases by disc electrophoresis has been developed.
    Type of Medium: Electronic Resource
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