Edward Levin

..Nicotine improves cognitive function in a number of animal models including rats, mice, monkeys, and recently, zebrafish. The zebrafish model allows higher throughput and ease in discovering mechanisms of cognitive improvement...

..Development of drugs that provide a net decrease in nicotinic receptor activity either through antagonism or desensitization could be worth exploring for beneficial effects for treating cognitive impairments...

..These receptors are a promising target for development of therapeutic treatments for a variety of diseases of cognitive impairment including Alzheimer's disease, attention deficit hyperactivity disorder (ADHD) and schizophrenia...

..Saz-A, which is a selective alpha4beta2-desensitizing agent and partial agonist, effectively reduces nicotine self-administration. This type of treatment holds promise for a new therapy to aid smoking cessation...

..This study showed that low doses of mecamylamine can effectively improve learning. A U-shaped dose-effect curve was documented. This suggests possible low-dose nicotinic antagonist lines of treatment for cognitive impairment...

..These results suggest that metallothioneins, through there roles in metal physiology or cellular protection, are involved in spatial learning and memory function...

..These data show that clozapine can cause memory impairment and it potentiates rather than reverses hippocampal lesion-induced deficits. There are critical sex-related differences in these effects...

..Nicotine has been shown in a variety of studies in humans and experimental animals to improve cognitive function. Nicotinic treatments are being developed as therapeutic treatments for cognitive dysfunction...

..Given that many antipsychotic drugs have substantial 5-HT2 antagonist effects, these atypical antipsychotic drugs may reduce the cognitive improvements caused by nicotinic treatments...

..Recently, we have found that nicotine also improves memory in zebrafish. Nicotinic agonists are being developed as novel treatments for Alzheimer's disease and other cognitive impairments...

..This study demonstrates persisting neurobehavioral effects of acute prenatal exposure to domoic acid at doses that do not cause overt clinical signs of toxicity...

..Novel EC-SOD mimetics may be useful in attenuating aging-induced cognitive impairments and other aspects of physiological decline with aging...

..Enhancement of EC-SOD activity appears to improve memory performance specifically in aging mice. EC-SOD mimetic treatment during the course of aging may hold promise for aging-induced cognitive impairment...

..Olanzapine caused a significant working memory impairment. Nicotine attenuated olanzapine-induced memory deficits. It may be the case that nicotinic co-treatment will be useful in addressing the cognitive impairment of schizophrenia...

..Thus it appears that antipsychotic drugs with actions blocking 5HT2 receptors may limit the efficacy of nicotinic co-treatments for cognitive enhancement...

..However, the sublethal persistent neurobehavioral toxicity appears to be less pervasive than reported effects following DA administered mid-gestation...

..Our results further characterize the long-term liabilities of maternal smoking but also point to the potential liabilities of nicotine-based treatments for smoking cessation during pregnancy...

..Adolescent-onset nicotine self-administration causes persistent increases in nicotine self-administration in female rats even after they reach adulthood and disrupts control over self-administration behavior...

..These studies support development of the 5-HT(2C) agonist lorcaserin to aid tobacco smoking cessation...

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..Animal models of attention can be effectively used for the development of new treatments of attentional impairment in ADHD and other syndromes in which have attentional impairments occur, such as Alzheimer's disease and schizophrenia...

..NMDA glutamate treatments may be particularly useful in helping lighter smokers successfully quit smoking, highlighting the need for diverse treatments for different types of smokers...

..H(1) antagonists may be a promising avenue to explore for new treatments to aid smoking cessation...

..This study demonstrates the sex-selective, long-term behavioral alterations caused by otherwise nontoxic neonatal exposure to parathion, with effects increasingly expressed with aging...

..This symposium organized by Edward Levin and Annette Kirshner, brought together researchers from the laboratories of Michael Aschner, Douglas Ruden, ..

..Patients with hippocampal beta2-containing nicotinic receptor loss may be well treated with clozapine therapy, while those with frontal cortical beta2-containing receptor loss may have a potentiated memory impairment caused by clozapine...

..5-HT mechanisms play critical roles in the maintenance of nicotine self-administration. Better understanding of those roles may help lead to new 5-HT-based treatments for tobacco addiction...

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..It is important to consider the interactions between nicotinic and antipsychotic drugs to develop the most efficacious treatment for cognitive improvement in people with schizophrenia...

..This may be relevant to the action of clozapine in attenuating sensory gating deficits in schizophrenia and may point to new avenues of treatment for sensory modulation disorders in which there is excessive tactile response...

..Sensory modulation deficit, which is a syndrome of sensory over-responsiveness may also benefit from such combination therapy...

..This not only provides information concerning the neural bases of cognitive performance, it also lends insight into new combination treatments for memory impairment...

..This model has demonstrated the cause-and-effect relationship between exposure to a hydrophilic toxin produced by P. piscicida and learning impairment, and specifically that the ventral hippocampus was critically involved...

..Lorr, & L. F. Droppleman, 1981). This small study (40 participants) provided evidence that nicotine treatment can reduce severity of attentional deficit symptoms and produce improvement on an objective computerized attention task...

..The atypical effects of lobeline may underlie its greater efficacy than nicotine for improving repeated acquisition. The effect of lobeline improving learning may be useful in the development of novel treatments for learning deficits...

..Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus uncovering the adaptive mechanisms that maintain basal performance...

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..These results support the involvement of alpha 4 beta 2 and alpha 7 nicotinic receptors in the ventral hippocampus as being critical for memory function...

..Studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction...

..05). Enhancement of EC-SOD activity appears to improve learning and memory performance, specifically in aging mice. EC-SOD mimetic treatment during the course of aging may hold promise for aging-induced cognitive impairment...

..Although the great majority of tobacco addiction begins during adolescence, little is known about differential nicotine effects in adolescents versus adults...

..These studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction...

..The molecular mechanisms by which early developmental CPF exposure produces these behavioral impairments expressed in adulthood can now be studied in the zebrafish model...

..Nicotine effects on other non-NMDA hippocampal receptor systems or extra-hippocampal systems may have been left unchecked by the diminished nicotinic effect on ventral hippocampal NMDA receptors...

..Nicotinic antagonistic treatment may be a useful new approach to treat cocaine addiction...

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..This study shows that nicotine affects memory function in zebrafish much like in rats, mice, monkeys and humans. Now, zebrafish can be used to help understand the molecular mechanisms crucial to nicotine effects on memory...

..Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus, uncovering the adaptive mechanisms that maintain basal performance...

..The molecular mechanisms by which early developmental CPF exposure produces these behavioral impairments expressed in adulthood can now be studied in the zebrafish model...

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..The identification of these functional deficits in zebrafish enables further studies with this model to determine how molecular and cellular mechanisms are disturbed to arrive at this compromised state...

..The resemblance of these findings to those of late gestational or neonatal CPF exposure indicates a prolonged window of vulnerability of brain development to CPF...

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..Our results indicate that neonatal CPF exposures, classically thought to be subtoxic, produce lasting changes in 5HT-related behaviors that resemble animal models of depression...

..Heterogeneity in response to nicotinic drugs given systemically may be due to anatomically distinct nicotinic systems in the brain and their unique roles in the neural bases of cognitive function...

..These studies demonstrate interactions between nicotine and antipsychotic drugs in terms of memory, which may have important impacts on the treatment of schizophrenia...

..This nicotine-induced anxiolytic effect was reversed by both MLA and DHbetaE, indicating that both nicotinic alpha7 and alpha4beta2 receptors are involved in the nicotinic effect on anxiety in zebrafish...

..Chronic nicotine effects on receptor regulation are significantly affected by concurrent blockade of NMDA glutamate receptors...

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..This may be helpful in screening for persisting neurobehavioral defects from a variety of toxicants...

..Both molecular/neurochemical and behavioral effects of developmental OP exposure have been seen at doses below those which cause appreciable cholinesterase inhibition...

..These results confirm the importance of alpha4beta2 and alpha7 nicotinic acetylcholine receptors in the dorsal hippocampus for appetitively-motivated spatial cognitive function...

..These results support the further investigation of nicotinic treatment as a promising therapy for AAMI...

..Our results are consistent with impaired fat utilization and prediabetes, as well as exposing a potential relationship between effects on fat metabolism and on synaptic function in the brain...

..The repeated acquisition test can help differentiate acute drug effects on learning. Nicotine and thioperamide effectively reversed each other's choice accuracy impairment even though each by itself impaired accuracy...

..This work shows that deleting metallothioneins increase the vulnerability to developmental mercury-induced neurocognitive impairment. Metallothionein effects on monoamine transmitters may be related to this cognitive effect...

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..Pyrilamine impaired working memory but improved reference memory in rats. Thus, H(1) antagonism seems to play a role in part of the beneficial actions of antipsychotics, such as clozapine...

..Unlike in the ventral hippocampus, the addition of DHbetaE to MLA in the basolateral amygdala significantly reduced the MLA-induced working memory deficit...

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..This study demonstrated the importance of NMDA glutamate systems in the amygdala for appetitively-motivated spatial memory performance...

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..Our results thus reinforce the concept that the adolescent brain is unusually receptive to the effects of nicotine in a manner that reinforces the potential for addiction...

..Nicotine-induced anxiolytic effects can be modeled in the zebrafish. This preparation will help in the investigation of the molecular bases of this effect...

..Our present behavioral study, together with the earlier in vitro study by Gay et al. (2008), suggests that effector domain MARCKS peptides could play a significant role in memory regulation and impairment...

..Furthermore, unlike the benzodiazepines, JNJ-5234801 does not have an adverse interaction with ethanol even at doses 20 to 40 times the minimal effective dose in the rat elevated plus maze (MED=1.0 mg/kg, p.o.)...

..Developmental exposures to organophosphate pesticides are virtually ubiquitous. These agents are neurotoxicants, but recent evidence also points to lasting effects on metabolism...

..In the current study, we explored the effects of nicotine and mecamylamine using an operant visual signal detection task designed to model sustained attention processes common to rats and humans...

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..In this study, we tested the impact of pretreatment with alcohol on subsequent alcohol drinking in outbred Sprague-Dawley and selectively bred alcohol-preferring (P) rats...

..Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound that potently and selectively desensitizes alpha4beta2 nicotinic receptors with only modest receptor activation...

..Clozapine was more detrimental than risperidone but the adverse effects of both clozapine and risperidone on attentional performance were masked in rats chronically treated with nicotine...

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..Chronic nicotine diminished the adverse effects of haloperidol on performance. This study establishes a paradigm to reliably determine the attentional impairment caused by antipsychotic drugs...

..5 days was noted. Behavioral test results suggest that embryonic exposure to DE-71 may alter activity level, fright response, predation rates, and learning ability in subsequent life stages...

..These preliminary results suggest that adolescent rats may have an increased sensitivity to nicotine and alcohol, which may consequently impact their initial addiction to these two drugs...

..In the developing brain, serotonin (5HT) systems are among the most sensitive to disruption by organophosphates...

..The effects on 5HT circuits expand the scope of behavioral endpoints that need to be considered in evaluating the developmental neurotoxicity of organophosphates...

..Thus, dietary factors may produce similar synaptic changes as do developmental neurotoxicants, potentially contributing to the increasing incidence of neurodevelopmental disorders...

..This study shows that dizocilpine reduces signal detection accuracy in a dose-dependent fashion. Nicotine can partially counteract an aspect of this reduction by reversing the dizocilpine-induced reduction of correct rejection...

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..Our results reinforce the conclusion that low dose exposure to different OPs can have quite different neurotoxic effects, obviously unconnected to their shared property as cholinesterase inhibitors...

..Organophosphates elicit developmental neurotoxicity through multiple mechanisms other than their shared property as cholinesterase inhibitors. Accordingly, these agents may differ in their effects on specific brain circuits...

..This interaction may be an important consideration for nicotine and ethanol coabuse and the possible therapeutic use of nicotinic drugs for memory dysfunction...

..For parathion, the threshold for lethality lies below that necessary for adverse effects on brain development, whereas the opposite is true for chlorpyrifos and diazinon...

..These findings further validate the operant visual signal detection task for assessing attentional impairments and their reversal...

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..The forum will provide an opportunity for methodological and theoretical issues to be integrated in the context of each talk as well as in a discussion session at the end of the symposium. ..

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