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Biomedical subjects

Edward D Levin

Publications and source records attributed to Edward D Levin.

At least 37 records · Page 2Linked to original sources
PubMed2005

Persisting behavioral consequences of prenatal domoic acid exposure in rats.

To investigate the behavioral effects of prenatal exposure to the marine toxin domoic acid, pregnant female rats were injected subcutaneously with 0, 0.3, 0.6, or 1.2 mg/kg of domoic acid on gestational day 13. The offspring were then run through a behavioral testing battery to determine the developmental effects of the toxin on spontaneous alternation in the T-maze, on locomotor activity in the Figure-8 maze, and on working memory in the 8-arm radial maze. In the T-maze, no significant domoic acid induced differences were seen on spontaneous alternation, but there were significant domoic acid effects on latency. Prenatal domoic acid exposure caused a dose-related increase in response latency in the second spontaneous alternation test. There was also a significant domoic acid effect seen in the 1-h long Figure-8 maze test. Locomotor activity measured in the Figure-8 maze detected a persisting effect of the 1.2 mg/kg domoic acid dose, which significantly increased the rate of habituation over the activity test session. This was characterized by higher initial activity followed by greater decline in activity. In the radial-arm maze the control vehicle treated rats showed the normal sex-related difference in spatial learning and memory with males outperforming females. Developmental domoic acid exposure decreased this effect such that the normal sex difference in spatial memory was not seen with the 1.2 mg/kg domoic acid dose. The rats of both sexes with a history of prenatal domoic acid exposure showed increased susceptibility to the amnestic effects of the muscarinic acetylcholine scopolamine, suggesting that they had less functional reserve with which to solve the radial-arm maze memory task. This study demonstrates persisting neurobehavioral effects of acute prenatal exposure to domoic acid at doses that do not cause overt clinical signs of toxicity.

Animals↗
PubMed2005

Developmental and behavioral effects of embryonic exposure to the polybrominated diphenylether mixture DE-71 in the killifish (Fundulus heteroclitus).

Exposures to penta polybrominated diphenylether (PeBDE) cause neurobehavioral toxicity in developing mice and rats. As levels of these ubiquitous contaminants are increasing in the environment, this raises concern that wildlife may also suffer such effects, with consequences for their ability to catch prey and avoid predators. PeBDE levels in wild-caught fish have been steadily escalating over the past fifteen years. To our knowledge, behavioral consequences of piscine embryonic exposure to PeBDE has not yet been studied. The objectives of this investigation were to characterize effects on development in an environmentally relevant fish model, and test for latent behavioral effects following cessation of exposure. Embryos from the estuarine minnow, Fundulus heteroclitus, were exposed from day 0-7 post fertilization to the industrial PeBDE mixture, DE-71 (0.001 to 100 microg l(-1)). Embryos were assayed for hatching success, development, and microsomal enzyme cytochrome P4501A (CYP1A) activity, which was determined by analysis of in ovo ethoxy-resorufin-O-deethylase (EROD) activation in embryos. Larval fish were assayed for predation ability, activity level, and fright response to a simulated predator. Juvenile fish were assayed for learning ability in a three-chambered fish maze. No induction of embryonic EROD activity was observed, nor was a high dose of DE-71 able to inhibit EROD activity induced by beta-naphthoflavone. No deformities were detected, but a subtle developmental asymmetry with respect to tail curvature direction was observed, and a hatching delay of up to 4.5 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.

Animals↗
PubMed2005

Chronic nicotine and dizocilpine effects on regionally specific nicotinic and NMDA glutamate receptor binding.

Chronic nicotine administration has long been known to increase the number of high-affinity alpha4beta2 nicotinic receptors with lesser effects on low-affinity alpha7 nicotinic receptors. Nicotine has been shown to promote the release of a variety of neurotransmitters including glutamate. Nicotine may also interact directly with the glutamatergic receptors. Nicotinic-glutamate interactions may be critical to the long-term effects of nicotine. Conversely, glutamatergic drugs may interact with the nicotinic system. Such interactions have important implications in interpretation of the mechanism of drug actions, especially when the drugs are given together. The current study examined the effects of chronic administration of nicotine (5 mg of the nicotine base/kg/day for 28 days), dizocilpine (MK-801) (0.3 mg/kg/day for 28 days), an NMDA receptor antagonist, as well as the combination of the two drugs on nicotinic and NMDA receptor densities in discrete brain regions. The chronic dose of dizocilpine used was behaviorally active causing a dramatic reduction in prepulse inhibition (PPI) of acoustic startle response. The nicotine dose used did not significantly affect PPI but previously we have found it to be behaviorally active in improving working memory function. High-affinity nicotinic receptor binding, as has been seen previously, was significantly increased by chronic nicotine in most areas. Chronic dizocilpine alone did not affect high-affinity nicotinic receptor binding, but it did modify the effects of chronic nicotine, attenuating nicotine-induced increases in the frontal cortex and striatum. Low-affinity nicotinic binding was significantly increased by chronic nicotine in only one area, the cerebellum. Chronic dizocilpine significantly increased low-affinity nicotinic binding in several brain areas, the colliculi, hippocampus, and the hypothalamus. The combination of nicotine and dizocilpine attenuated the effects of each with diminished nicotine-induced increased nicotinic low-affinity binding in the cerebellum and diminished dizocilpine-induced increased nicotinic low-affinity binding in the hippocampus and hypothalamus. In contrast, chronic nicotine and dizocilpine had a mutually potentiating effect of increasing nicotinic low-affinity binding in the frontal cortex. NMDA receptor binding was affected only in the hippocampus, where both dizocilpine and nicotine significantly increased binding. Chronic nicotine effects on receptor regulation are significantly affected by concurrent blockade of NMDA glutamate receptors.

Allosteric Regulation↗
PubMed2005

Olanzapine interactions with nicotine and mecamylamine in rats: effects on memory function.

Olanzapine is a widely used atypical antipsychotic drug. It is quite effective in reducing psychotic symptoms. However, the syndrome of schizophrenia encompasses more than psychosis. There is a pronounced cognitive impairment among other negative neurobehavioral symptoms. Classic antipsychotic drugs such as haloperidol do not alleviate cognitive impairment associated with schizophrenia and have been shown to exacerbate the dysfunction. The atypical antipsychotic drugs have a different profile of receptor actions and may have a different array of actions on cognitive function. The purpose of the current studies was to determine the effects of olanzapine on working memory function as measured by choice accuracy in the radial-arm maze. In determining the cognitive effects of any antipsychotic drug it is critical to determine its interactions with nicotinic manipulations since the great majority of people with schizophrenia smoke cigarettes and alterations in nicotinic receptors have been found in people with schizophrenia. 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.

Animals↗
PubMed2005

Nicotinic-serotonergic drug interactions and attentional performance in rats.

RATIONALE: Both central serotonergic and nicotinic systems play important roles in a variety of neurobehavioral functions; however, the interactions of these two systems have not been fully characterized. The current study served to determine the impact of a relatively selective 5-HT2A receptor antagonist, ketanserin, on attentional function in rats and the interactions of ketanserin with nicotine administration. METHODS: A standard operant visual signal detection task was used to assess sustained attention. In expt 1, adult female Sprague-Dawley rats (n = 39) were injected subcutaneously (SC) with a dose range of ketanserin (0, 0.25, 0.5 and 1 mg/kg). In expt 2, the interactions of acute ketanserin (0, 1 and 2 mg/kg, SC) and acute nicotine (0, 25 and 50 microg/kg, SC) were assessed. In expt 3, the interaction of acute ketanserin (0, 1 and 2 mg/kg, SC) and chronic nicotine (5 mg/kg per day, SC for 4 weeks via osmotic pump) was characterized. Using an operant visual signal detection task, three possible outcomes (dependent variables) were measured in each trial: percent hit, percent correct rejection, and response omissions. RESULTS: Ketanserin, when given alone, did not have a significant effect on either percent hit or percent correct rejection. Acute administration of 25 microg/kg nicotine significantly improved percent hit (i.e. improvement in choice accuracy), an effect that was reversed by acute administration of 1 mg/kg ketanserin. Chronic nicotine infusion for 28 consecutive days significantly increased percent correct rejection (i.e. improvement in choice accuracy) without development of tolerance, an effect which was reversed by an acute dose of 2 mg/kg ketanserin. CONCLUSIONS: These data suggest a functional interaction between nicotine and 5-HT2A receptor antagonist ketanserin.

Animals↗
PubMed2005

Memory decline of aging reduced by extracellular superoxide dismutase overexpression.

Extracellular superoxide dismutase (EC-SOD) plays an important role in controlling oxidative stress as well as intercellular signaling. In the current study, we tested the effect of EC-SOD overexpression over the lifespan of a set of mice and their wild-type controls to determine the time scale over which EC-SOD overexpression might attenuate aging-induced memory impairment. Mice with overexpression of EC-SOD and wild-type controls were initially trained on the radial-arm maze as young adults (3-5 months) and then retrained during middle age (12-14 months) and retested in old age at 27 and 30 months. There was little EC-SOD effect during the young adult middle age periods. EC-SOD overexpression prevented the decline in choice accuracy when the mice were 27-30 months of age. The EC-SOD overexpressing mice maintained their performance, while the wild-type mice declined to naïve levels of performance by 30 months of age. 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.

Aging↗
PubMed2005

Nicotine and clozapine actions on pre-pulse inhibition deficits caused by N-methyl-D-aspartate (NMDA) glutamatergic receptor blockade.

Pre-pulse inhibition (PPI) is a phenomenon of neurobehavioral plasticity in which the motor response to a startling stimulus is inhibited by a preceding stimulus of a lower intensity. Most often this is tested in the auditory mode. PPI is impaired in a variety of clinical states, most notably schizophrenia. PPI is easily modeled in experimental animals and serves as a useful basis for determining the neural bases for behavioral plasticity. In the current study we examined the interactions of N-methyl-D-aspartate (NMDA) glutamate and nicotinic cholinergic receptor systems in the expression of PPI. Female Sprague-Dawley rats were tested for auditory PPI after s.c. injections of the NMDA antagonist dizocilpine (also known as MK-801), the prototypic nicotinic agonist nicotine or both. Vehicle (saline) injections served as the control. Nicotine (0.2-0.8 mg/kg) by itself caused a modest but significant dose-related improvement in PPI. Dizocilpine (25-100 microg/kg) caused a dramatic dose-related impairment in PPI. Interestingly, the low to moderate doses of nicotine potentiated the PPI impairment by dizocilpine. In a second experiment nicotine and dizocilpine interactions with the atypical antipsychotic drug clozapine were assessed. As in the first experiment, nicotine potentiated the adverse effects of dizocilpine on PPI. The combination of nicotine with clozapine effectively attenuated the PPI impairment caused by dizocilpine when neither alone was effective. Inasmuch as PPI is impaired in schizophrenia, its reversal by the antipsychotic drug clozapine may depend on co-administration of nicotine by smoking in the patients. Development of nicotinic-based co-treatments for schizophrenia may achieve this benefit of nicotine without the hazards of smoking. Sensory modulation deficit, which is a syndrome of sensory over-responsiveness may also benefit from such combination therapy.

Animals↗
PubMed2005

Reversal of clozapine effects on working memory in rats with fimbria-fornix lesions.

Clozapine is an effective antipsychotic drug, but its effects on cognitive function are unclear. Previously, we found that clozapine caused a working memory deficit, which was reversed by nicotine. Hippocampal systems are important in determining clozapine effect on memory. In the current study, the memory effects of clozapine and nicotine administration were determined in rats with lesions of the fimbria-fornix, a fiber bundle which carries cholinergic and other projections between the septum and the hippocampus. Female Sprague-Dawley rats were trained on a win-shift procedure in the radial-arm maze, in which each arm entry was rewarded once per session. Then, 13 rats received bilateral knife-cut lesions of the fimbria-fornix, while 14 rats underwent sham surgery. The rats were tested after subcutaneous injections with combinations of clozapine (0 and 1.25 mg/kg) and nicotine (0, 0.2, and 0.4 mg/kg). In sham-operated rats, clozapine caused a significant (P<0.005) working memory impairment. Fimbria-fornix lesions also caused a significant (P<0.05) memory impairment. Interestingly, clozapine had the opposite effect on working memory in the lesioned vs sham-operated rats. In contrast to its effects in controls, clozapine (1.25 mg/kg) significantly (P<0.05) attenuated the working memory deficit caused by fimbria-fornix lesions. Nicotine (0.2 mg/kg) did not quite significantly improve memory in lesioned rats. The effects of clozapine and nicotine were not additive in the lesioned rats. This study demonstrates the efficacy of clozapine in improving working memory in fimbria-fornix-lesioned rats, whereas it causes impairments in intact rats. Therapeutic treatment with clozapine in people with malfunctions of the hippocampus such as seen in schizophrenia may improve cognitive performance, whereas the same doses of clozapine may impair memory in individuals without hippocampal malfunction.

Animals↗
PubMed2005

Gestational dexamethasone treatment elicits sex-dependent alterations in locomotor activity, reward-based memory and hippocampal cholinergic function in adolescent and adult rats.

Glucocorticoids are the consensus treatment for preventing respiratory distress syndrome in preterm infants but there is emerging evidence of subsequent neurobehavioral abnormalities, independent of somatic growth effects. Pregnant rats were given 0.2 mg/kg of dexamethasone, a dose commensurate with clinical use, on gestational days 17-19 and behavioral evaluations were made on the offspring in adolescence and adulthood. The dexamethasone groups had the same body weights as the controls but nevertheless displayed long-term, sex-selective alterations in locomotor and cognitive behaviors. In the figure-8 activity apparatus, dexamethasone treatment ablated the normal sex differences in locomotor activity by reducing values in females to the lower level typical of males; habituation of activity similarly was impaired in females, reducing the profile to match that of control males, while male rats in the dexamethasone group showed a partially feminized pattern of habituation. In the 8-arm radial maze, control rats displayed typical sex differences, with male rats performing more accurately than females. Dexamethasone treatment eliminated this normal dichotomy, delaying learning in males while improving performance in females to the level normally seen in control males. Finally, we assessed hippocampal [3H]hemicholinium-3 binding as a biomarker for cholinergic synaptic activity, and again found loss of sex differences in the dexamethasone group: values in males were increased to the higher levels typical of females. These results indicate that gestational treatment with dexamethasone obtunds the normal sex differences in neurochemistry and behavior that are typically seen in adolescence in adulthood, thus producing sex-selective alterations in activity, learning, and memory.

Acetylcholine↗
PubMed2005

Adolescent vulnerabilities to chronic alcohol or nicotine exposure: findings from rodent models.

This article presents an overview of the proceedings from a symposium entitled "Is adolescence special? Possible age-related vulnerabilities to chronic alcohol or nicotine exposure," organized by Susan Barron and Linda Spear and held at the 2004 Research Society on Alcoholism Meeting in Vancouver, British Columbia. This symposium, co-sponsored by the Fetal Alcohol Syndrome Study Group and the Neurobehavioral Teratology Society, focused on our current knowledge regarding the long-term consequences of ethanol and/or nicotine exposure during adolescence with the emphasis on data from rodent models. The support from these two societies represents the understanding by these research groups that adolescence represents a unique developmental stage for the effects of chronic drug exposure and also marks an age in which many risky behaviors including alcohol consumption and smoking typically begin. The speakers included (1) Aaron White, who presented data on the effects of adolescent ethanol exposure on subsequent motor or cognitive response to an ethanol challenge in adulthood; (2) Richard Bell, who presented data suggesting that genetic differences could play a role in adolescent vulnerability to ethanol; (3) Craig Slawecki, who presented data looking at the effects of chronic exposure to alcohol or nicotine on neurophysiologic and behavioral end points; and (4) Ed Levin, who presented data on acute and long-term consequences of adolescent nicotine exposure. Finally, Linda Spear provided some summary points and recommendations regarding unresolved issues and future directions.

Adolescent↗
PubMed2005

Developmental exposure of rats to chlorpyrifos leads to behavioral alterations in adulthood, involving serotonergic mechanisms and resembling animal models of depression.

Developmental exposure to chlorpyrifos (CPF) causes persistent changes in serotonergic (5HT) systems. We administered 1 mg/kg/day CPF to rats on postnatal days 1-4, a regimen below the threshold for systemic toxicity. When tested in adulthood, CPF-exposed animals showed abnormalities in behavioral tests that involve 5HT mechanisms. In the elevated plus maze, males treated with CPF spent more time in the open arms, an effect seen with 5HT deficiencies in animal models of depression. Similarly, in an anhedonia test, the CPF-exposed group showed a decreased preference for chocolate milk versus water. Developmental CPF exposure also has lasting effects on cognitive function. We replicated our earlier finding that developmental CPF exposure ablates the normal sex differences in 16-arm radial maze learning and memory: during acquisition training, control male rats typically perform more accurately than do control females, but CPF treatment eliminated this normal sex difference. Females exposed to CPF showed a reduction in working and reference memory errors down to the rate of control males. Conversely, CPF-exposed males exhibited an increase in working and reference memory errors. After radial-arm acquisition training, we assessed the role of 5HT by challenging the animals with the 5HT2 receptor antagonist ketanserin. Ketanserin did not affect performance in controls but elicited dose-dependent increases in working and reference memory errors in the CPF group, indicating an abnormal dependence on 5HT systems. 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.

Animals↗
PubMed2005

Extracellular superoxide dismutase (EC-SOD) quenches free radicals and attenuates age-related cognitive decline: opportunities for novel drug development in aging.

Superoxide dismutase (SOD) is one of the most effective mechanisms in physiology for inactivating reactive oxygen species. Elevated SOD activity can be therapeutically useful by protecting against oxidative stress-induced neurotoxicity. Acutely increased extracellular-SOD (EC-SOD) activity protects against neurobehavioral impairment caused by acute ischemia. Chronically increased EC-SOD activity may also be therapeutically useful by protecting against chronic oxidative stress-induced neurobehavioral damage that accumulates during the aging process. We have found that mice with genetic overexpression of EC-SOD do not show the aging-induced decline in learning and memory that control, wild type mice show. From 14-22 months of age, the EC-SOD overexpressing mice have significantly better spatial learning working memory function than that of controls. This effect is specific to the aging period. Young adult EC-SOD overexpressing mice do not have better learning and memory function than controls. The beneficial effects of increased EC-SOD activity with aging may be achieved without risk of impairment during younger ages by chronically administering EC-SOD mimetics from mature adulthood into the aging period. Novel EC-SOD mimetics may be useful in attenuating aging-induced cognitive impairments and other aspects of physiological decline with aging.

Aging↗
PubMed2004

Nicotine-antipsychotic drug interactions and attentional performance in female rats.

Schizophrenia is marked by pronounced cognitive impairments in addition to the hallmark psychotic symptoms like hallucinations. Antipsychotic drugs can effectively reduce these hallucinations; however, the drugs have not resolved the cognitive impairment. Interestingly, nicotine, a drug commonly self-administered by people with schizophrenia, has been shown to significantly improve cognitive function of people with schizophrenia. The current study was conducted to determine the effect of typical (haloperidol) and atypical (clozapine and risperidone) antipsychotic drug treatment on sustained attention in rats performing a visual signal detection task. In addition, the interaction of haloperidol with chronic nicotine administration was assessed. Female Sprague-Dawley rats were injected subcutaneously with clozapine (0, 0.6, 1.25 and 2.5 mg/kg), risperidone (0, 0.025, 0.05 and 0.1 mg/kg) or haloperidol (0, 0.01, 0.02 and 0.04 mg/kg). In the second part of the study, the interaction of acute haloperidol (0, 0.005, 0.01 and 0.02 mg/kg) and chronic nicotine (5 mg/kg/day, for 4 weeks via osmotic minipump) was characterized. Clozapine, risperidone and haloperidol all caused dose-related impairments in percent hit performance. There was a significant linear dose-related impairment in percent hit caused by risperidone. All the doses of clozapine caused a significant impairment in percent hit at the higher luminance intensities in the visual signal detection task. The 0.01 and 0.02 mg/kg haloperidol doses caused significant decreases in percent hit. The 0.04 mg/kg haloperidol dose impaired performance of the task to the point that reliable choice accuracy measurements could not be made. Chronic nicotine infusion significantly diminished the impairing effects of haloperidol on performance during weeks 1-2. In summary, both typical and atypical antipsychotic drugs significantly impaired sustained attention in rats. Haloperidol was more detrimental than clozapine and risperidone. 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.

Animals↗
PubMed2004

Baclofen interactions with nicotine in rats: effects on memory.

Nicotine has been shown in numerous previous studies to significantly improve memory on the radial-arm maze, yet the critical mechanisms underlying this effect are not fully characterized. Nicotine stimulates the release of a number of neurotransmitters important for memory function including (gamma-aminobutyric acid) GABA. The importance of nicotinic-GABA interactions regarding memory is currently unknown. The purpose of the current study was to determine the interactive effects of nicotine and the GABA agonist baclofen on working memory function as measured by choice accuracy in the radial-arm maze. Female Sprague-Dawley rats trained to asymptotic performance levels on a win-shift eight-arm radial maze task were used for assessment of nicotine-baclofen interactions. Low doses of baclofen improved memory performance while higher doses impaired it. Nicotine, as seen before, improved memory performance. Nicotine also significantly reversed the higher dose baclofen-induced deficit. These data show the importance of both nicotinic and GABA systems in working memory function and the interactions between these two transmitter receptor systems. This not only provides information concerning the neural bases of cognitive performance, it also lends insight into new combination treatments for memory impairment.

Animals↗
PubMed2003

Chronic transdermal nicotine patch treatment effects on cognitive performance in age-associated memory impairment.

OBJECTIVES: Chronic transdermal nicotine has been found to improve attentional performance in patients with Alzheimer's disease (AD), but little is known about chronic nicotine effects in age-associated memory impairment (AAMI), a milder form of cognitive dysfunction. The current study was performed to determine the clinical and neuropsychological effects of chronic transdermal nicotine in AAMI subjects over a 4-week period. DESIGN: The double-blind, placebo-controlled, cross-over study consisted of two 4-week periods separated by a 2-week washout period. SETTING: An outpatient setting was used. PARTICIPANTS: The subjects ( n=11) met criteria for AAMI. INTERVENTIONS: The subjects were given nicotine patches (Nicotrol) to wear for 16 h a day at the following doses: 5 mg/day during week 1, 10 mg/day during week 2 and week 3 and 5 mg/day during week 4. MEASUREMENTS: The effects of nicotine treatment were determined with the clinical global impressions questionnaire, Conners' Continuous Performance test, and the automated neuropsychologic assessment metrics (ANAM) computerized neuropsychology battery. RESULTS: Nicotine significantly improved the clinical global impression score as assessed by participants, as well as objective tests of attentional function on the Connors' Continuous Performance Test and decision reaction time on the neuropsychology test battery. Nicotine did not improve performance on other tests measuring motor and memory function. CONCLUSION: Chronic transdermal nicotine treatment in AAMI subjects caused a sustained improvement in clinical symptoms and objective computerized tests of attention. These results support the further investigation of nicotinic treatment as a promising therapy for AAMI.

Administration, Cutaneous↗
PubMed2003

Ventral hippocampal NMDA blockade and nicotinic effects on memory function.

Nicotinic acetylcholine and NMDA glutamate receptors play critical roles in memory function. The brain areas involved in their interaction are still under investigation. One likely area is the hippocampus. Ventral hippocampal administration of nicotinic antagonists impair memory. Hippocampal administration of NMDA antagonists also cause memory impairments. We evaluated the importance of ventral hippocampal NMDA receptors for nicotinic actions on memory by testing the impact of systemic nicotine on memory with and without administration of the NMDA antagonist dizocilpine into the ventral hippocampus. Sprague-Dawley rats (N=11) trained on the 16-arm radial maze were bilaterally implanted with local infusion cannulae in the ventral hippocampus. The effects on memory function of ventral hippocampal infusions of 0, 2, 6 and 18 microg per side of dizocilpine were examined with and without acute systemic nicotine administration (0 or 0.4 mg/kg). The dizocilpine doses tested did not cause memory deficits by themselves but only did so when given in combination with systemic nicotine. Blocking NMDA ventral hippocampal actions revealed an impairing action of nicotine on memory. 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.

Animals↗
PubMed2003

Heterogeneity of toxicant response: sources of human variability.

While risk assessment models attempt to predict human risk to toxicant exposure, in many cases these models cannot account for the wide variety of human responses. This review addresses several primary sources of heterogeneity that may affect individual responses to drug or toxicant exposure. Consideration was given to genetic polymorphisms, age-related factors during development and senescence, gender differences associated with hormonal function, and preexisting diseases influenced by toxicant exposure. These selected examples demonstrate the need for additional steps in risk assessment that are needed to more accurately predict human responses to toxicants and drugs.

Age Factors↗