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Edward D Levin

Publications and source records attributed to Edward D Levin.

At least 55 records · Page 3Linked to original sources
PubMed2003

Adolescent-onset nicotine self-administration modeled in female rats.

RATIONALE: Although the great majority of tobacco addiction begins during adolescence, little is known about differential nicotine effects in adolescents versus adults. OBJECTIVES: A rat model was used to determine the impact of the age of onset on nicotine self-administration. METHODS: In expt 1, nicotine self-administration of female Sprague-Dawley rats over a range of acute doses (0.01-0.08 mg/kg per infusion) was determined in adolescent (beginning at 54-62 days) versus adult (beginning at 84-90 days). In expt 2, chronic nicotine self-administration over 4 weeks from adolescence into adulthood was compared with the chronic self-administration beginning in adulthood. In expt 3, adolescent-adult differences in nicotine effects on body temperature and locomotor responses were determined. RESULTS: Adolescent-onset rats showed a significant main effect of increased nicotine intake compared with adult-onset rats in an eight-fold range of acute unit doses/infusion. Significant age differences were also seen in the chronic level of nicotine self-administration. Over 4 weeks, the adolescent-onset group had nearly double the rate of nicotine self-administration of the benchmark nicotine dose (0.03 mg/kg per infusion) compared to the adult-onset group. This increased nicotine intake persisted into adulthood. Adolescent rats had significantly greater response than adults to the hypothermic effects of nicotine, but had significantly less response than adults to the reduction in locomotor activity seen after nicotine. CONCLUSIONS: Adolescent-onset nicotine self-administration in female rats was associated with significantly higher levels of nicotine self-administration versus rats, which began nicotine self-administration in adulthood. This greater self-administration persists into adulthood and may underlie greater propensity of adolescents to nicotine addiction.

Adolescent↗
PubMed2003

Nicotinic-glutamatergic interactions and attentional performance on an operant visual signal detection task in female rats.

Nicotinic systems have been shown to be critically involved in cognitive function including attention. Nicotine has been shown to improve performance on attentional tasks in humans with Alzheimer's disease, schizophrenia and attention deficit hyperactivity disorder. Nicotine has mixed effects on attentional accuracy in unimpaired rats with findings of increased, reduced or unaltered accuracy under different conditions. Nicotine effects on attentional function in rats might be more clearly seen in reversing impaired performance. The current study determined nicotine effects on attentional accuracy reduced by the NMDA receptor antagonist dizocilpine (MK-801). Sprague-Dawley rats (N=35) were trained on a food-motivated two-lever operant task with one lever correct after a brief visual signal (0.027-1.22 lx) for hits and the other lever correct after the absence of a signal for correct rejections. First, a dose response study of dizocilpine was conducted to determine the threshold for impairment. The rats were administered acute doses of dizocilpine (0, 12.5, 25 and 50 microg/kg, sc). The 50 microg/kg dose caused significant (p<0.0005) reduction in percent hit at the four highest signal intensities. Percent correct rejection was also significantly lowered by this dose (p<0.005). No effect was seen with 12.5 microg/kg and only minimal effect seen with 25 microg/kg. Then, nicotine-dizocilpine interactions were investigated. The rats were administered acute doses of dizocilpine (0, 37.5 and 50 microg/kg, sc) and nicotine (0, 25 and 50 microg/kg, sc), alone or in combination. Percent hit was affected by nicotine and dizocilpine in a complex fashion with only the nicotinexdizocilpinexsignal intensity interaction being significant (p<0.05). Percent correct rejection showed a more straightforward effect. Percent correct rejection was significantly reduced by 50 microg/kg dizocilpine (p<0.025). The addition of 25 microg/kg of nicotine significantly (p<0.025) reversed the dizocilpine-induced reduction of correct rejection. 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.

Animals↗
PubMed2003

Reliabilities and intercorrelations of reported and objective measures of smoking in patients with schizophrenia.

We examined the test-retest reliabilities of reported and objective measures of smoking, and the intercorrelations among these measures, in acutely psychotic patients with schizophrenia to determine whether severe psychiatric illness affects the utility of these variables. All measures demonstrated good test-retest reliability. Objective measures of smoking were consistently intercorrelated and should be the preferred outcome measures in studies testing strategies to reduce smoking.

Adult↗
PubMed2003

Nicotine-alcohol interactions and attentional performance on an operant visual signal detection task in female rats.

Nicotine and alcohol are very often co-used and co-abused. Thus, it is important to understand their interactions. In many ways, nicotine and alcohol have opposing effects. This can be clearly seen in terms of their effects on cognitive function. Nicotine effectively improves attention while alcohol impairs it. The current study was conducted to determine in a rat model the interaction of nicotine and alcohol on attention using an operant visual signal detection task. It is hypothesized that nicotine would reverse the alcohol-induced impairment in accuracy of performance in this task. Female Sprague-Dawley rats (N=35) were trained on a visual operant signal detection task for food reinforcement with 300 trials/session in three equal time blocks. The rats were divided into poor and good performers according to their predrug baseline performance accuracy. The first experiment examined the dose-effect function of alcohol (0, 0.375, and 0.75 g/kg i.p.) on this task. The lower alcohol dose significantly impaired percent correct rejection in the high-performing rats but not the low-performing rats. The higher alcohol dose significantly impaired percent hit performance during the first two thirds of the session in both high- and low-performing groups. The second experiment examined alcohol (0.75 g/kg i.p.) interactions with nicotine (0, 12.5, 25, and 50 microg/kg s.c.) on attentional performance. The 25 and 50 microg/kg nicotine doses caused a significant (P<.05) improvement in hit accuracy. Alcohol blocked this nicotine-induced improvement, even though at this later time it no longer had an effect of its own. In the high baseline group, the 25 microg/kg nicotine dose also caused a significant (P<.025) improvement in hit accuracy. As in Experiment 1, the high baseline group was not significantly impaired by 0.75 g/kg of alcohol. However, this alcohol dose did eliminate the nicotine-induced improvement. These results suggest that alcohol, when given alone, impairs sustained attention and blocks nicotine-induced attentional improvements even when it does not cause impairments on its own.

Animals↗
PubMed2003

Lobeline-induced learning improvement of rats in the radial-arm maze.

Lobeline is a nicotinic ligand with some nicotine-like effects, but with some atypical effects as well, including actions as a nicotinic antagonist. Lobeline, like nicotine, has been found to significantly improve memory function as well as provide anxiolytic-like effects in the elevated plus maze. Lobeline effects on learning remain to be fully characterized. Nicotine has been found to improve learning of shock avoidance tasks. Other nicotinic agonists also have been shown to improve learning performance. However, this effect is limited. In some tasks, nicotine has been found to cause deficits. In the current study, effects of lobeline and nicotine injections were assessed in a repeated acquisition procedure in the radial-arm maze for 3 weeks of drug administration. Lobeline (0.3 and 0.9 mg/kg) improved learning on the radial-arm maze. Neither nicotine dose (0.1 and 0.3 mg/kg) improved learning. This nicotine dose range was previously found to improve post-acquisition working memory performance in the radial-arm maze. 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.

Animals↗
PubMed2003

Nicotinic mechanisms of memory: effects of acute local DHbetaE and MLA infusions in the basolateral amygdala.

Nicotine has been shown to improve working memory. The neural mechanisms underlying this effect are still being determined. The ventral hippocampus is critical for nicotinic effects on memory. Local ventral hippocampal infusions of either the nicotinic alpha7 nicotinic receptor antagonist methyllycaconitine (MLA) or the alpha4beta2 nicotinic receptor antagonist dihydro-beta-erythroidine (DHbetaE) caused working memory impairments, but no additive effects were seen. Other areas, such as the amygdala, also likely play important roles in nicotinic effects on memory. Amygdalar lesions cause memory impairment and there is a dense concentration of nicotinic receptors in the basolateral amygdala. The current study used local basolateral amygdalar infusions of the nicotinic antagonists MLA and DHbetaE to determine the involvement of alpha7 and alpha4beta2 nicotinic receptors in spatial working and reference memory. Rats (n=8) were trained in the 16-arm radial maze and were implanted with bilateral infusion cannulae into the basolateral amygdala. Acute infusions of MLA (6.75 micro g/side, P<0.0005) or DHbetaE (3.38 micro g/side, P<0.025) caused significant working memory impairments. When given together MLA and DHbetaE did not produce an additive effect. In fact, the 6.75 micro g/kg dose of DHbetaE produced a significant (P<0.0005) attenuation of the MLA-induced working memory impairment. Significant effects were not seen with reference memory or response latency. Nicotinic systems in the basolateral amygdala, as in the ventral hippocampus, are important for spatial working memory. In both the basolateral amygdala and the ventral hippocampus, MLA and DHbetaE individually caused working memory impairments. The lowest effective dose of DHbetaE was lower in the basolateral amygdala than in the ventral hippocampus. In both the basolateral amygdala and the ventral hippocampus, combined MLA and DHbetaE treatment did not produce additive working memory deficits. Unlike in the ventral hippocampus, the addition of DHbetaE to MLA in the basolateral amygdala significantly reduced the MLA-induced working memory deficit.

Aconitine↗
PubMed2003

NMDA systems in the amygdala and piriform cortex and nicotinic effects on memory function.

Both nicotinic cholinergic and NMDA glutaminergic systems are important for memory function. Nicotine has been found repeatedly to significantly improve working memory performance in the radial-arm maze. The NMDA antagonist dizocilpine has been found to impair working memory performance. There is neuropharmacological evidence that these two systems are functionally related. Nicotine is potent at releasing many transmitters including glutamate. The current study was conducted to examine the interaction of nicotinic and NMDA systems within the amygdala with regard to working and reference memory. Rats were trained on a working/reference procedure on a 16-arm radial maze. After acquisition, local infusion cannulae were implanted bilaterally into the amygdala and piriform cortex using stereotaxic techniques. Then 20 min prior to running the rats on the radial-arm maze, they were injected subcutaneously with (-) nicotine ditartrate at doses of 0 and 0.4 mg/kg. Following this, the rats received local infusions of (+) dizocilpine maleate (MK-801) at doses of 0, 2, 6 and 18 microg per side into the lateral amygdala or piriform cortex 10 min prior to running on the radial-arm maze. Each of the eight nicotine and dizocilpine combinations was administered to each rat in a counterbalanced order. After completion of the drug sessions the rats were sacrificed, and using histological methods the cannulae placements were verified. Acute amygdalar infusions of the NMDA glutamate receptor antagonist dizocilpine induced dose-related working and reference memory deficits in the radial-arm maze. Systemic nicotine was not seen to reverse these effects. Dizocilpine infusions into the adjacent piriform cortex did not impair memory function, supporting the specificity of dizocilpine effects in the amygdala. Latency effects were seen with both drugs in both areas. Latencies were decreased with both systemic nicotine and dizocilpine in both the lateral amygdala and the piriform cortex. This study demonstrated the importance of NMDA glutamate systems in the amygdala for appetitively-motivated spatial memory performance.

Amygdala↗
PubMed2002

Effects of nicotine and mecamylamine on choice accuracy in an operant visual signal detection task in female rats.

RATIONALE: During the past decade, central nicotinic systems have been shown in both experimental animals and humans to play an important role in cognitive function. However, the way in which specific aspects of cognitive function are affected by nicotinic systems has remained unclear. In humans, the most pronounced action of nicotine is to improve attention, but in rats, memory improvement is more easily seen. This may be due to differences in methods for assessing attention in rats and humans or to species differences in the roles of nicotinic systems in cognitive function. 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. METHODS: Adult female rats ( n=35) were trained to perform the signal detection task to a stable baseline of about 75% accuracy. The rats were then assigned to two subgroups of high and low accuracy based on overall accuracy (hits and correct rejections) at the end of training. All rats were then injected (SC, 10 min before testing) with saline or different doses of nicotine (0.0125, 0.025, 0.05, 0.1, 0.2 and 0.4 mg/kg) or the nicotinic antagonist mecamylamine (1, 2 and 4 mg/kg). RESULTS: A low dose range of nicotine (0.0125, 0.025, and 0.05 mg/kg) caused a dose-related increase in percent correct rejection. This dose range did not affect correct detections of the signal (percent hit). Higher doses of nicotine (0.1, 0.2 and 0.4 mg/kg) did not affect percent correct rejection, but did have a time-dependent effect on percent hit. Early in the session, the higher doses of nicotine reduced percent hit, whereas during the later part of the session higher doses of nicotine increased percent hit. Effects of nicotine did not differ between the high- and low-accuracy rats. Mecamylamine decreased choice accuracy, reducing both percent hit and percent correct rejection. Mecamylamine reduced percent hit in the low-accuracy rats at a lower drug dose than in the high-accuracy rats. CONCLUSIONS: These results support the involvement of nicotinic systems in attention in rats, as has been shown in humans. This rat model of sustained attention may provide a good approach to studying neural mechanisms underlying the effects of nicotinic cholinergic receptors on attention and a means to evaluate the potential of novel nicotinic agonists to counteract attentional dysfunction.

Animals↗
PubMed2002

Nicotinic receptor subtypes and cognitive function.

Nicotinic receptor systems are involved in a wide variety of behavioral functions including cognitive function. Nicotinic medications may provide beneficial treatment for cognitive dysfunction such as Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Nicotine has been shown to improve attentional performance in all of these disorders. Better efficacy with fewer side effects might be achieved with novel nicotinic ligands selective for particular nicotinic subtypes. To develop these novel selective nicotinic ligands it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function. Nicotine-induced cognitive improvement in rats is most consistently seen in working memory tasks. We have found that both acute and chronic nicotine administration significantly improves working memory performance of rats in the radial-arm maze. The pharmacologic and anatomic mechanisms for this effect have been examined in our laboratory in a series of local drug infusion studies. Both alpha 4 beta 2 and alpha 7 nicotinic receptors in the ventral hippocampus and basolateral amygdala are involved in working memory function. Working memory impairments were caused by local infusion of either alpha 4 beta 2 or alpha 7 antagonists. Ventral hippocampal alpha 4 beta 2 blockade-induced working memory deficits are reversed by chronic systemic nicotine treatment, while ventral hippocampal alpha 7 blockade-induced working memory deficits were not found to be reversed by the same nicotine regimen. Interestingly, alpha 4 beta 2 and alpha 7 induced deficits were not found to be additive in either the ventral hippocampus or the basolateral amygdala. In fact, in the amygdala, alpha 7 antagonist cotreatment actually reversed the working memory impairment caused by alpha 4 beta 2 antagonist administration. 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.

Amygdala↗
PubMed2002

Nicotine-alcohol interactions and cognitive function in rats.

Nicotine and ethanol are the most widely abused drugs in the world. They are very often used and abused together. However, little is known about the functional interaction of nicotine and ethanol. The current project studied the interactive effects of nicotine and ethanol on working memory in the eight-arm radial maze. Adult female rats were trained on a radial arm maze for 18 sessions to reach asymptotic levels of choice accuracy. During the maintenance phase of radial arm maze testing, which indexed working memory function, the rats were injected with nicotine (0, 0.15, 0.3, 0.6, and 1.2 mg/kg sc, 20 min before testing) with and without ethanol pretreatment (0 or 1.5 g/kg, 16% v/v ip, 30 min before testing). All animals received the treatments in a counterbalanced order with at least 1 week between treatments. Higher doses of nicotine had a significant interaction with ethanol in terms of radial arm maze choice accuracy. Nicotine plus ethanol coadministration precipitated a significant choice accuracy impairment at doses that when given alone had no effect on performance. At the lower dose range of nicotine, ethanol coadministration eliminated the nicotine-induced memory improvement. No significant effects were seen with either nicotine or ethanol treatment or their interaction on response latency in the radial arm maze. The nicotine-ethanol interactive effects on memory were compared with the interaction of their well-characterized hypothermic effects. Nicotine and alcohol, when injected separately or in combination, induced hypothermia with no significant interactive effect. This study found that ethanol blocked low-dose nicotine-induced memory improvement and precipitated memory impairment with high-dose nicotine treatment. This interaction may be an important consideration for nicotine and ethanol coabuse and the possible therapeutic use of nicotinic drugs for memory dysfunction.

Animals↗
PubMed2002

Nicotine interactions with haloperidol, clozapine and risperidone and working memory function in rats.

Nicotine has been shown in a variety of studies to improve memory performance. The cognitive effects of nicotine are particularly important with regard to schizophrenia. In the current studies nicotine interactions with three different antipsychotic drugs, haloperidol, clozapine and risperidone, were assessed with regard to memory function. Female Sprague-Dawley rats were trained on the radial-arm maze to asymptotic levels of choice accuracy. They were then administered nicotine alone or in combination with haloperidol, clozapine or risperidone. Acute haloperidol (0.04 mg/kg) did not by itself affect memory performance. Co-administration of haloperidol with nicotine, however, decreased memory performance compared with nicotine administration in isolation. Acute clozapine (1.25 and 2.5 mg/kg) caused a significant memory impairment, an effect reversed by acute nicotine co-treatment. Risperidone (0.05 mg/kg), like haloperidol, did not by itself affect memory performance. Risperidone co-administration with nicotine, however, did significantly attenuate the improvement caused by nicotine administration in isolation. The similar interaction of haloperidol and risperidone with nicotine may be due to their common action of blocking D(2) receptors, a mechanism of action not shared by clozapine. In contrast to the interaction of nicotine with haloperidol or risperidone, nicotine effectively reversed clozapine-induced memory impairment. These studies demonstrate interactions between nicotine and antipsychotic drugs in terms of memory, which may have important impacts on the treatment of schizophrenia.

Animals↗
PubMed2002

Extracellular superoxide dismutase overexpression protects against aging-induced cognitive impairment in mice.

Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide and appears to play a role in controlling oxidative stress and intercellular signaling. Whether EC-SOD overexpression would help or hinder neurobehavioral function appears to depend on the age of the individual. In young adult mice, we have found that EC-SOD overexpression can interfere with learning on the radial-arm maze, possibly by reducing control over nitric oxide neurotransmission. In aged mice, we found, in the current study, that EC-SOD overexpression greatly improves learning on the radial-arm maze. Control (N = 17) and EC-SOD overexpressing mice (N = 13) acquired the 8-arm radial maze over 21 sessions of training. The EC-SOD overexpressing mice had significantly better choice accuracy than the control mice (p < 0.005). The EC-SOD overexpressing mice averaged 6.34+/-0.22 correct arm entries before an error (entries to repeat) during the acquisition phase, while the control mice averaged 5.18+/-0.22 entries to repeat. EC-SOD genotype did not cause a main effect on response latency. The advantage held by the EC-SOD overexpressing mice persisted during the eight-session post-acquisition phase of testing (p < 0.01). When there was a shift from high to low levels of motivation by reducing the period of food restriction before testing, the EC-SOD overexpression-induced improvement was reduced slightly, but it was still significant compared with the wild-type controls (p < 0.025). Then, after 4 months of no testing, the mice were tested for retention and reacquisition of performance on the radial-arm maze. The EC-SOD overexpressing mice maintained their significantly better choice accuracy (p < 0.05). 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.

Aging↗
PubMed2001

Chronic inhibition of alpha4beta2 nicotinic receptors in the ventral hippocampus of rats: impacts on memory and nicotine response.

RATIONALE: Acute and chronic systemic nicotine administration has been shown to cause significant spatial memory improvement. The critical nicotinic receptor subtypes for this effect and their location are still being determined. Nicotinic receptors in the ventral hippocampus have been found to be critically involved in memory. Acute ventral hippocampal infusions of dihydro-beta-erythroidine (DHbetaE), an alpha4beta2 nicotinic receptor antagonist, impaired spatial memory of rats in the radial-arm maze. OBJECTIVES: The current study used chronic ventral hippocampal infusion of DHbetaE as a model of nicotinic receptor loss such as that which occurs in Alzheimer's disease. The therapeutic effect of systemic nicotine treatment in reversing the DHbetaE-induced memory impairment was determined. METHODS: Rats were pretrained to asymptotic levels of performance on the eight-arm radial maze. Then, they were implanted with bilateral infusion cannulae in the ventral hippocampus, through which 0, 33.3, or 100 microg/side/day of DHbetaE was continuously infused for 4 weeks. The rats were retested on the eight-arm maze throughout infusion period and after withdrawal, and the interaction of acute systemic nicotine injections on memory was tested. RESULTS: The higher (100 microg/side/day) but not the lower (33.3 microg/side/day) DHbetaE dose caused a significant spatial memory impairment. Acute systemic nicotine injections (0, 0.1, 0.2, and 0.4 mg/kg, subcutaneous) attenuated the memory impairing effects of 100 microg/side/day of DHbetaE. There was no significant effect on response latency with the chronic DHbetaE infusion. Acute systemic nicotine infusions did significantly speed responding, an effect which was reversed by chronic hippocampal infusions of DHbetaE. After withdrawal there were no significant lasting effects on choice accuracy or response latency. Wet-dog shakes were significantly elevated during chronic hippocampal DHbetaE administration with no effect during the withdrawal period. CONCLUSIONS: These results indicate that chronic inhibition of a subset of nicotinic receptors in the hippocampus results in a significant impairment in the spatial memory choice accuracy. The ability of nicotine to attenuate the impairment supports the development of nicotinic agonist therapy of syndromes, such as Alzheimer's disease, that involve a chronic decrease in the activity of the alpha4beta2 nicotinic receptors and memory impairment.

Alzheimer Disease↗
PubMedDate not supplied

Adolescent and adult rats respond differently to nicotine and alcohol: motor activity and body temperature.

Alcohol and nicotine are the most widely abused drugs in the world. The use of these addictive drugs often begins in adolescence, however, little is known about the different impacts of nicotine and alcohol on adolescents versus adults. This study examined both the individual and combined effects of nicotine and alcohol on body temperature and locomotor activity in adolescent and adults rats. Rats were injected with saline (SC) + saline (IP), nicotine (SC) + saline (IP), alcohol (IP) + saline (SC) or alcohol (IP) + nicotine (SC). The dose selected for nicotine was 0.2 mg/kg and for alcohol 2.5 g/kg (16% v/v). For each age/treatment, 10-13 animals were used, with each animal receiving only one treatment. In regards to body temperature, both nicotine and alcohol caused a significant age x drug interaction. The combination of nicotine and alcohol caused greater drop in body temperature in adolescent than in adult rats. Neither of the two drugs, when given alone, caused differential effects in adolescents or adult rats, though both resulted in drop in body temperature. In terms of locomotor activity, the treatment that produced a significantly different effect between adolescents and adults was nicotine alone. Nicotine significantly decreased locomotor activity in adolescent compared to adult rats. 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.

Adaptation, Physiological↗
PubMedDate not supplied

Behavioral alterations in adolescent and adult rats caused by a brief subtoxic exposure to chlorpyrifos during neurulation.

The widely used organophosphate insecticide, chlorpyrifos (CPF), elicits neurobehavioral abnormalities after apparently subtoxic neonatal exposures. In the current study, we administered 1 or 5 mg/kg/day of CPF to pregnant rats on gestational days 9-12, the embryonic phase spanning formation and closure of the neural tube. Although there were no effects on growth or viability, offspring showed behavioral abnormalities when tested in adolescence and adulthood. In the CPF-exposed groups, locomotor hyperactivity was noted in early T-maze trials, and in the elevated plus-maze; alterations in the rate of habituation were also identified. Learning and memory were adversely affected, as assessed using the 16-arm radial maze. Although all CPF-exposed animals eventually learned the task, reference and working memory were impaired in the early training sessions. After training, rats in the CPF group did not show the characteristic amnestic effect of scopolamine, a muscarinic acetylcholine antagonist, suggesting that, unlike the situation in the control group, muscarinic pathways were not used to solve the maze. These results indicate that apparently subtoxic CPF exposure during neurulation adversely affects brain development, leading to behavioral anomalies that selectively include impairment of cholinergic circuits used in learning and memory. 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.

Animals↗
PubMedDate not supplied

Neurobehavioral assessment of mice after developmental AZT exposure.

Azidothymidine (AZT) is administered to pregnant women with HIV to prevent the spread of infection to their fetuses. Since gestation is a period of critical neurodevelopment, it is important to determine the risk AZT exposure may pose to neurobehavioral function of the offspring. The current study focused on teratological risks of developmental AZT exposure to neurocognitive function. Male and female Swiss mice were administered AZT or vehicle (0, 100, or 200 mg/kg/day po given twice daily in equal amounts for 32 weeks before and during gestation). Adult male and female offspring (n = 10/sex/treatment group) underwent neurobehavioral testing focused on determining learning and memory capabilities in the radial-arm maze. AZT exposure did not cause significant deficits during radial-arm maze acquisition. No impairment was seen in asymptotic levels of choice accuracy indicative of working memory function. Attempts to unmask subtle learning impairments following developmental AZT by the introduction of behavioral challenges such as reduction of motivational state (food restriction either 4-6 h or 22-24 h) or imposition of intrasession delays of 1.5 min to 2.5 h were unsuccessful. With a 4-week intersession delay, a significant AZT Treatment x Delay effect was seen with a significantly greater decline seen in the controls as compared to the 100 mg/kg/day AZT group. Locomotor activity on the radial-arm maze was significantly affected by AZT treatment (100 mg/kg/day) during the acquisition phase, but not during the other test phases. No behavioral alterations were seen related to stress as measured by the elevated plus maze. Vestibulomotor functioning on the balance beam remained unaltered. Using an extended dosing regimen including dosing of both sires and dams, as well as placing a greater demand on reproductive system performance with three continuous breedings, this study detected only subtle neurobehavioral impairments in mice after prenatal AZT exposure at clinically relevant doses.

Age Factors↗
PubMedDate not supplied

Nicotinic involvement in memory function in zebrafish.

Zebrafish are an emerging model for the study of the molecular mechanisms of brain function. To conduct studies of the neural bases of behavior in zebrafish, we must understand the behavioral function of zebrafish and how it is altered by perturbations of brain function. This study determined nicotine actions on memory function in zebrafish. With the methods that we have developed to assess memory in zebrafish using delayed spatial alternation (DSA), we determined the dose effect function of acute nicotine on memory function in zebrafish. As in rodents and primates, low nicotine doses improve memory in zebrafish, while high nicotine doses have diminished effect and can impair memory. 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.

Acetylcholine↗