Biomedical subjects

Edward D Levin

Publications and source records attributed to Edward D Levin.

15 recordsLinked to original sources

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↗

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

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

Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations.

Use of chlorpyrifos (CPF) has been curtailed due to its developmental neurotoxicity. In rats, postnatal CPF administration produces lasting changes in cognitive performance, but less information is available about the effects of prenatal exposure. We administered CPF to pregnant rats on gestational days (GD) 17-20, a peak period of neurogenesis, using doses (1 or 5 mg/kg/day) below the threshold for fetal growth impairment. We then evaluated performance in the T-maze, Figure-8 apparatus and 16-arm radial maze, beginning in adolescence and continuing into adulthood. CPF elicited initial locomotor hyperactivity in the T-maze. Females showed slower habituation in the Fig. 8 maze; no effects were seen in males. In the radial-arm maze, females showed impaired choice accuracy for both working and reference memory and again, males were unaffected. Despite the deficits, all animals eventually learned the maze with continued training. At that point, we challenged them with the muscarinic antagonist, scopolamine, to determine the dependence of behavioral performance on cholinergic function. Whereas control females showed impairment with scopolamine, CPF-exposed females did not, implying that the delayed acquisition of the task had been accomplished through alternative mechanisms. The differences were specific to muscarinic circuits, as control and CPF groups responded similarly to the nicotinic antagonist, mecamylamine. Surprisingly, adverse effects of CPF were greater in the group receiving 1 mg/kg as compared to 5 mg/kg. Promotional effects of acetylcholine (ACh) on cell differentiation may thus help to offset CPF-induced developmental damage that occurs through other noncholinergic mechanisms. Our results indicate that late prenatal exposure to CPF induces long-term changes in cognitive performance that are distinctly gender-selective. Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus, uncovering the adaptive mechanisms that maintain basal performance.

Animals↗

PubMedDate not supplied

Chlorpyrifos exposure of developing zebrafish: effects on survival and long-term effects on response latency and spatial discrimination.

Chlorpyrifos (CPF) is a widely used insecticide, which has been shown to interfere with neurobehavioral development. Rat models have been key in demonstrating that prenatal CPF exposure causes choice accuracy deficits and motor alterations, which persist into adulthood. Complementary nonmammalian models can be useful in determining the molecular mechanisms underlying the persisting behavioral effects of developmental CPF exposure. Zebrafish with their clear chorion and extensive developmental information base provide an excellent model for assessment of molecular processes of toxicant impacted neurodevelopment. To facilitate the use of the zebrafish model and to compare it to the more typical rodent models, the behavioral phenotype of CPF toxicity in zebrafish must be well characterized. Our laboratory has developed methods for assessing spatial discrimination learning in zebrafish, which can differentiate response latency from choice accuracy in a three chambered fish tank. Low and high doses of CPF (10 and 100 ng/ml on days 1-5 postfertilization) both had significant persisting effects on both spatial discrimination and response latency over 18 weeks of testing. The high, but not the low dose, significantly accelerated mortality rates of the fish during the study from 20-38 weeks of age. Developmental exposure to either 10 or 100 ng/ml of CPF caused significant spatial discrimination impairments in zebrafish when they were adults. The impairment caused by 10 ng/ml was seen during early but not later testing, while the impairment caused by 100 ng/ml became more pronounced with continued testing. The higher dose caused a more pervasive impairment. The 10 and 100 ng/ml doses had opposite effects on response latency. The low 10 ng/ml dose significantly slowed response latency, while the high 100 ng/ml dose significant increased response latency. Both of these effects diminished with continued testing. CPF exposure during early development caused clear behavioral impairments, which lasted throughout adulthood in zebrafish. The molecular mechanisms by which early developmental CPF exposure produces these behavioral impairments expressed in adulthood can now be studied in the zebrafish model.

Animals↗

PubMedDate not supplied

Learning impairment caused by a toxin produced by Pfiesteria piscicida infused into the hippocampus of rats.

Pfiesteria piscicida, an estuarine dinoflagellate, which has been shown to kill fish, has also been associated with neurocognitive deficits in humans. With a rat model, we have demonstrated the cause-and-effect relationship between Pfiesteria exposure and learning impairment. In several studies, we have replicated the finding in Sprague-Dawley rats that exposure to fixed acute doses of Pfiesteria cells or filtrates caused radial-arm maze learning impairment. Recently, this finding of Pfiesteria-induced learning impairment in rats has been independently replicated in another laboratory as well. We have demonstrated significant Pfiesteria-induced learning impairment in both the win-shift and repeated-acquisition tasks in the radial-arm maze and in reversal learning in a visual operant signal detection task. These learning impairments have been seen as long as 10 weeks after a single acute exposure to Pfiesteria. In the current study, we used a hydrophilic toxin isolated from clonal P. piscicida cultures (PfTx) and tested its effect when applied locally to the ventral hippocampus on repeated acquisition of rats in the radial-arm maze. Toxin exposure impaired choice accuracy in the radial-arm maze repeated acquisition procedure. The PfTx-induced impairment was seen at the beginning of the session and the early learning deficit was persistent across 6 weeks of testing after a single administration of the toxin. Eventually, with enough practice, in each session, the PfTx-exposed rats did learn that session's problem as did control rats. 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.

Animals↗