Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat lines were selected by breeding for sensitivity to signs of autonomic stimulation (hypotherma, loss of body weight, and reduced water intake) induced by the cholinesterase inhibitor diisopropyl fluorophosphate (DFP). These lines have since been maintained for 10 generations by continued selection for hypothermic responsiveness to the muscarinic agonist oxotremorine. The sensitive rats (Flinders Sensitive Line, FSL) differ from the resistant rats (Flinders Resistant Line, FRL) both neurochemically and behaviorally, particularly in aversively motivated test situations in which response speed is assessed. This study was conducted to determine whether the selected differences in cholinergic autonomic sensitivity would be expressed as differences in cognitive ability based on choice accuracy in appetitive tasks. The working and reference memory of rats of these two strains was thus assessed using operant delayed matching-to-position/visual discrimination (DMTP/VD) and the radial-arm maze. A Long-Evans (L-E) reference group was included in the DMTP/VD study. FSL rats responded more slowly than the other rats during acquisition of both tasks, but showed no differences in response accuracy either during acquisition or during asymptotic performance of either task. In addition, challenges with muscarinic and nicotinic antagonists and agonists [scopolamine (0.06-1.0 mg/kg), pilocarpine (1.0-4.0 mg/kg), mecamylamine (1.0-10.0 mg/kg), and nicotine (0.1-0.3 mg/kg)] demonstrated predicted differences in sensitivity among the lines only on performance measures such as response latency and trial completion. Counter to prediction, the sensitivity of the FRL rats to the ability of scopolamine to reduce matching accuracy was lower than those of the L-E and FSL rats. Thus selection based upon physiological endpoints related to cholinergic autonomic homeostasis did not produce analogous differences in cognitive function in rats.
Neurobiol Learn Mem 1995 Mar
PMID:Spatial working and reference memory in rats bred for autonomic sensitivity to cholinergic stimulation: acquisition, accuracy, speed, and effects of cholinergic drugs. 766 85

Past research indicates that the anticholinergic drug scopolamine disrupts memory and environmentally induced hypoalgesia in rats. The present study examined the impact of the centrally active cholinesterase inhibitor physostigmine, which enhances memory and central cholinergic activity, on brief shock-induced hypoalgesia on the tail-flick test using Sprague-Dawley rats. It is reported that physostigmine (0.1 mg/kg) potentiates the magnitude of this hypoalgesia. Contrary to past research, our results showed that omission of baseline testing did not eliminate hypoalgesia or its potentiation by physostigmine. Similar to its effects on memory, physostigmine (0.04, 0.1, and 0.25 mg/kg) has a nonmonotonic impact on brief shock-induced hypoalgesia; low doses potentiated hypoalgesia (0.1 mg/kg), whereas a high dose (0.25 mg/kg) disrupted it. These results provide further evidence that the cholinergic system indirectly affects pain reactivity by modulating the memory of the aversive event.
Neurobiol Learn Mem 1998 Nov
PMID:Physostigmine's impact on brief shock-induced hypoalgesia parallels its effect on memory. 977 28

Four cholinesterase inhibitors have been approved by the US Food and Drug Administration for treating behavioral symptoms of Alzheimer's disease. Here we review our experiences with two cholinesterase inhibitors (metrifonate and galanthamine) and a muscarinic acetylcholine receptor agonist (CI-1017) in behavioral pharmacological and brain slice experiments in aging and young rabbits. Aging rabbits are impaired in their ability to acquire the hippocampus-dependent trace eyeblink conditioning task, as compared to young controls. A large proportion of aging animals cannot reach behavioral criterion in this task. Those that do learn, do so more slowly. In addition, the post-burst afterhyperpolarization and spike frequency accommodation is increased in hippocampal pyramidal neurons from aging animals, i.e., cellular excitability is reduced as compared to those from young animals. Metrifonate, galanthamine, and CI-1017 reduced the learning deficits observed in aging rabbits so that they learned almost as quickly as young controls. These cholinergic compounds also enhanced the postsynaptic excitability of hippocampal pyramidal neurons in vitro. Therefore, we propose that the amelioration of learning impairment with the cholinergic compounds may in part be due to the enhanced excitability of hippocampal pyramidal neurons. The potential relevance of our studies to further understanding the cellular and behavioral changes that occur with normal aging and Alzheimer's Disease is discussed.
Neurobiol Learn Mem 2003 Nov
PMID:Modulation of cholinergic transmission enhances excitability of hippocampal pyramidal neurons and ameliorates learning impairments in aging animals. 1452 65

The present experiments were aimed at determining whether acetylcholine (ACh) plays a role in encoding and retrieval of spatial information using a modified Hebb-Williams maze. In addition, the present experiments tested two computational models of hippocampal function during encoding and retrieval using a maze sensitive to hippocampal disruption. Thirty male, Long-Evans rats served as subjects. Chronic cannulae were implanted bilaterally into the CA3 (n=26) and CA1 (n=5) subregions of the hippocampus. Rats were tested using a modified Hebb-Williams maze. In the first experiment, rats were injected with either saline or scopolamine hydrobromide 10 min before testing for each day. The number of errors made per day per group was used as the measure of learning. Encoding was assessed by the average number of errors made on the first five trials of Day 1 compared to the last five trials of Day 1, whereas the average number of errors made on the first five trials of Day 2 compared to the last five trials of Day I was used to assess retrieval. No deficit was found for the saline group. The scopolamine group showed a deficit in encoding, but not retrieval. In the second experiment, rats were injected with either saline or physostigmine 10 min before testing each day. In contrast to the scopolamine groups, the physostigmine group showed a deficit in retrieval, but not encoding. To test whether the retrieval deficit was due to a disruption in storage or gaining access to the information two groups of rats received either saline on Day 1 and physostigmine on Day 2 or physostigmine on Day 1 and saline on Day 2. In addition, one group received physostigmine immediately after testing on Day 1. Data indicate that physostigmine causes a disruption of retrieval by means of a disruption in consolidation process. In conclusion, the cholinergic antagonist, scopolamine, disrupts encoding in both CA3 and CA1 subregions of the hippocampus. Furthermore, the cholinesterase inhibitor, physostigmine, boosts ACh action during a time when cholinergic levels need to decline for proper consolidation.
Neurobiol Learn Mem 2003 Nov
PMID:Cholinergic modulation of the hippocampus during encoding and retrieval. 1452 75

Cholinergic systems are critical to the neural mechanisms mediating learning. Reduced nicotinic cholinergic receptor (nAChR) binding is a hallmark of normal aging. These reductions are markedly more severe in some dementias, such as Alzheimer's disease. Pharmacological central nervous system therapies are a means to ameliorate the cognitive deficits associated with normal aging and aging-related dementias. Trace eyeblink conditioning (EBC), a hippocampus- and forebrain-dependent learning paradigm, is impaired in both aged rabbits and aged humans, attributable in part to cholinergic dysfunction. In the present study, we examined the effects of galantamine (3 mg/kg), a cholinesterase inhibitor and nAChR allosteric potentiating ligand, on the acquisition of trace EBC in aged (30-33 months) and young (2-3 months) female rabbits. Trace EBC involves the association of a conditioned stimulus (CS) with an unconditioned stimulus (US), separated by a stimulus-free trace interval. Repeated CS-US pairings results in the development of the conditioned eyeblink response (CR) prior to US onset. Aged rabbits receiving daily injections of galantamine (Aged/Gal) exhibited significant improvements compared with age-matched controls in trials to eight CRs in 10 trial block criterion (P = 0.0402) as well as performance across 20 d of training [F(1,21) = 5.114, P = 0.0345]. Mean onset and peak latency of CRs exhibited by Aged/Gal rabbits also differed significantly [F(1,21) = 6.120/6.582, P = 0.0220/0.0180, respectively] compared with age-matched controls, resembling more closely CR timing of young drug and control rabbits. Galantamine did not improve acquisition rates in young rabbits compared with age-matched controls. These data indicate that by enhancing nicotinic and muscarinic transmission, galantamine is effective in offsetting the learning deficits associated with decreased cholinergic transmission in the aging brain.
Learn Mem
PMID:Galantamine facilitates acquisition of hippocampus-dependent trace eyeblink conditioning in aged rabbits. 1474 24

The manuscript describes a study on the blood cholinesterase (ChE) level in an exposed population at different interval of time after spraying with malathion suspension (SRES) use for kala-azar vector control in an endemic area of Bihar, India. The toxicity of a 5% malathion formulation in the form of a slow release emulsified suspension (SRES) was assessed by measuring serum ChE levels in spraymen and in the exposed population. The study showed a significant decrease in ChE levels in the spraymen (p < 0.01) after one week of spraying and in exposed population one week and one month after of spraying (p < 0.01), but was still within the normal range of ChE concentration, one year after spraying, the ChE concentration in the exposed population was the same as prior to spraying (p > 0.01). On no occasion was the decrease in ChE level alarming. A parallel examination of the clinical status also showed the absence of any over toxicity or any behavioural changes in the exposed population. Hence, it may be concluded that 5% malathion slow release formulation, SRES, is a safe insecticide for use as a vector control measure in endemic areas of kala-azar in Bihar, India so long as good personal protection for spraymen is provided to minimize absorption and it can substitute the presently used traditional DDT spray.
Mem Inst Oswaldo Cruz 2004 Mar
PMID:Evaluation of cholinesterase level in an endemic population exposed to malathion suspension formulation as a vector control measure. 1525 Apr 79

Deltamethrin and other pyrethroids have been extensively used in Argentina since 1980, for the chemical control of Triatoma infestans Klug (Hemiptera: Reduviidae). Recently, resistance to deltamethrin was detected in field populations by the survival of bugs exposed by topical application to the diagnostic dose estimated on the CIPEIN susceptible strain. Results of the current study showed low resistant ratios (RRs) to deltamethrin for the resistant populations (RR ranged from 2.0 for San Luis colony to 7.9 for Salta colony). Biochemical studies were made on the most resistant colony (Salta) and the susceptible strain (CIPEIN), in order to establish the importance of degradative mechanisms as a cause of the detected resistance. Esterase activity was measured on 3 days old first instars through phenylthioacetate and a-naphtyl acetate activities. The results showed a significant difference in no cholinesterase esterase activity from susceptible (7.6 +/- 0,7 micro M S./i.min.) and Salta resistant colony (9.5 +/- 0.8 microM S./i.min.). Cytochrome p450 mono-oxygenase (p450) activity was measured on individual insects through ethoxycoumarine deethylase (ECOD) activity using a fluorescence microplate reader. The dependence of ECOD activity on age and body region of the nymphs, and pH and time of incubation were studied in order to optimize the measurement. As a result, comparative studies were performed on abdomens of 2 days old first instars at pH 7.2 and 4 h incubation time. ECOD activity of first nymphs was significantly lower in the susceptible colony (61.3 +/- 9.08 pg ECOD/ insect) than in the resistant one (108.1+/- 5.7 pg ECOD/ insect). These results suggest that degradative esterases (no-cholinesterase) and mono-oxygenases cytochrome p450, play an important role in the resistance to deltamethrin in Salta colony from Argentina.
Mem Inst Oswaldo Cruz 2004 May
PMID:Role of enhanced detoxication in a deltamethrin-resistant population of Triatoma infestans (Hemiptera, Reduviidae) from Argentina. 1527 11

In most studies comparing trace and delay conditioning, CS duration is kept constant across training conditions but the interstimulus interval (ISI), the time from CS onset to US onset, is confounded. In the infrequently used long-delay condition, however, ISI is kept constant across the trace and delay conditions but CS duration varies. A recent study reported that trace and long-delay fear conditioning have the same developmental trajectory, with both emerging later in development than standard-delay conditioning (). Past studies have shown that trace conditioning is mediated by the cholinergic system; given the parallel developmental emergence of trace and long-delay conditioning, the present study examined whether the cholinergic system also mediates long-delay conditioning. Two experiments, both involving Sprague-Dawley-derived rats and using freezing as a measure of learned fear, showed that the cholinergic system is critically involved in trace conditioning but is not involved in long-delay conditioning. Specifically, pre-training injections of the muscarinic receptor antagonist scopolamine impaired acquisition of a CS-US association in 32-day-old rats trained with a trace procedure but had no effect on rats this age trained with a long-delay procedure (Experiment 1). Similarly, pre-training injections of physostigmine, a cholinesterase inhibitor, enhanced acquisition of trace conditioning in 25-day-old rats but had no effect on long-delay conditioning in rats this age (Experiment 2). Taken together, the results indicate that despite the similarities between trace and long-delay conditioning in terms of developmental emergence and level of conditioned responding, they are mediated by different physiological systems.
Neurobiol Learn Mem 2007 Jan
PMID:Pharmacological dissociation of trace and long-delay fear conditioning in young rats. 1690 19

Previous work in our laboratory demonstrated that galantamine, a cholinesterase inhibitor and weak cholinergic agonist, facilitated classical trace eyeblink conditioning in healthy, young rabbits [Simon, B. B., Knuckley, B., & Powell, D. A. (2004). Galantamine facilitates acquisition of a trace-conditioned eyeblink response in healthy, young rabbits. Learning & Memory, 11(1), 116-122.]. The current study investigated the effects of galantamine (0.0 or 3.0mg/kg) in rabbits sustaining knife-cut lesions to the fimbria-fornix, a major projection pathway connecting the hippocampus to cortical and subcortical brain structures involved in the formation of long-term memories. Two experiments were conducted. Experiment one assessed the effects of knife-cut lesions to the fornix or sham surgeries on trace eyeblink (EB) conditioning. Results indicate that fornix lesions significantly retarded EB conditioning when trace parameters were employed. Experiment 2 assessed whether treatment with galantamine would reverse the deficits caused by fornix damage. Results indicate that 3.0mg/kg GAL reversed trace EB conditioning deficits in animals with fornix knife-cut lesions. These findings suggest that galantamine may provide benefit in the reversal of cognitive dysfunction following certain types of brain damage, especially damage involving hippocampal structures.
Neurobiol Learn Mem 2007 Oct
PMID:Impairments in trace EB conditioning by knife-cut lesions to the fornix in rabbits: reversal by galantamine. 1761 52

Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer's disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22-25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 microg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice.
Neurobiol Learn Mem 2008 Feb
PMID:Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome. 1764 30


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