Maze Choice Research Articles

Novelty during rearing increased inquisitive exploration but was not related to early ranging behavior of laying hens

Range use by free-range laying hen flocks is heterogeneous. We hypothesized that ranging behaviour may be motivated by curiosity and thwarted by fearfulness. This project aimed to increase a hen’s motivation to explore by enriching the rearing environment and identify relationships between exploration, fear and ranging. Day-old Hy-Line chicks (n = 1700) were reared in environments that provided novel items, structures for perching or an industry standard floor rearing environment. Prior to range access, fear and exploratory behaviors were assessed at 18 weeks of age (cohort 1; n = 30 hens/treatment) via novel arena and novel object tests and at 22 weeks of age (cohort 2; n = 30 hens/treatment) using an 8-arm radial maze choice paradigm adapted from previous rodent research. Hens were trained to expect success in two arms (reward) and failure in two arms (mild punishment), the remaining four arms (ambiguous arms) were not available during training. After training, all hens were retested for 8 minutes with access to the four familiar arms only, then for four minutes with access to the ambiguous arms for the first time, in addition to the success and failure arms. Latency to enter the ambiguous arms and the number of ambiguous arms entered were assessed as an indicator of a hen’s willingness to forgo reward and risk punishment to explore a novel area. At 25 weeks of age, hens were provided with range access and individual range access was monitored for three weeks. Latency to access the range and the number of days the range was accessed was not related to rearing treatment (p > 0.05) and was only weakly correlated with behavior during the novel arena, novel object and 8-arm radial maze tests (r < 0.3). However, hens reared in the novelty rearing environment were more willing to forgo reward to explore the ambiguous arms than hens reared in the control environment (p = 0.004). We did not identify strong evidence that exploration or fearfulness was related to early ranging behavior. However, we show that motivation to explore increases when hens are reared in an enriched environment.

NMDA receptor blockade in the dorsolateral striatum impairs consolidation but not retrieval of habit memory

The present study investigated whether N-methyl-d-aspartate (NMDA) receptors in the dorsolateral striatum (DLS) mediate consolidation and retrieval of habit memory. Adult male Long-Evans rats were trained in a response learning version of a water plus-maze task in which rats were reinforced to make a habitual and consistent body-turn response at the maze choice point in order to mount a hidden escape platform. Prior research indicates that acquisition, consolidation, and retrieval in this task requires DLS function. The present study consisted of two experiments. In Experiment 1, rats received intra-DLS post-training injections of the NMDA receptor antagonist 2-amino-5- phosphonopentanoic acid (AP5; 2 µg/side) to examine the role of NMDA receptors in consolidation of habit memory. In Experiment 2, different groups of rats received a single pre-retrieval injection of AP5 in the DLS (AP5; 2 µg/side) during the last day of maze training to examine the potential role of NMDA receptors in retrieval of habit memory. Results indicated that post-training intra-DLS AP5 injections impaired memory consolidation. However, administration of AP5 at the same dose that impaired consolidation had no effect on memory retrieval. The findings are consistent with previous research indicating a role for NMDA receptors in the DLS in memory consolidation, and suggest that NMDA-dependent synaptic activity in the DLS may not be a critical component of habit memory retrieval.

Effects of manganese exposure on crayfish motility.

Manganese (Mn) is a metal ion that is essential for healthy brain functioning at low levels (Quintanar, 2008). However, excessive exposure to Mn can lead to manganism — a neurodegenerative disease that manifests in Parkinsonian symptoms. High levels of Mn are found in hazardous occupational environments, especially in the mining and welding industries. In addition to the Parkinsonian symptoms associated with exposure to high levels of Mn, low to moderate Mn exposure has been linked with subtle impairments, such as hyperactivity and decreased cognitive abilities (Neal and Zheng, 2015). These low to moderate exposures can occur due to unregulated Mn levels in public tap water, which is especially prone to infiltration of neurotoxic chemicals in regions with high levels of mining activity (Quintanar, 2008). It was hypothesized that low to moderate Mn exposure in crayfish would be associated with altered motility in a T-maze. Crayfish exposed to varying levels of Mn were tested in a two-arm T-maze with a lighted arm and a dark arm. Movements and behavior were analyzed with video tracking software EthoVision XT 11. Behaviors of interest, including place preference to maze zones, choice behaviors, and general activity levels were recorded. We expect that Mn exposure will be associated with significant deficits in crayfish motility, which can be inferred to affect decision-making and risk-taking behaviors.

Functional connectivity changes during a working memory task in rat via NMF analysis.

Working memory (WM) is necessary in higher cognition. The brain as a complex network is formed by interconnections among neurons. Connectivity results in neural dynamics to support cognition. The first aim is to investigate connectivity dynamics in medial prefrontal cortex (mPFC) networks during WM. As brain neural activity is sparse, the second aim is to find the intrinsic connectivity property in a feature space. Using multi-channel electrode recording techniques, spikes were simultaneously obtained from mPFC of rats that performed a Y-maze WM task. Continuous time series converted from spikes were embedded in a low-dimensional space by non-negative matrix factorization (NMF). mPFC network in original space was constructed by measuring connections among neurons. And the same network in NMF space was constructed by computing connectivity values between the extracted NMF components. Causal density (Cd) and global efficiency (E) were estimated to present the network property. The results showed that Cd and E significantly peaked in the interval right before the maze choice point in correct trials. However, the increase did not emerge in error trials. Additionally, Cd and E in two spaces displayed similar trends in correct trials. The difference was that the measures in NMF space were significantly greater than those in original space. Our findings indicated that the anticipatory changes in mPFC networks may have an effect on future WM behavioral choices. Moreover, the NMF analysis achieves a better characterization for a brain network.

The Effects of Using Different Procedures to Score Maze Measures

The purpose of this study was to examine how different scoring procedures affect interpretation of maze curriculum‐based measurements. Fall and spring data were collected from 199 students receiving supplemental reading instruction. Maze probes were scored first by counting all correct maze choices, followed by four scoring variations designed to reduce the effect of random guessing. Pearson's r correlation coefficients were calculated among scoring procedures and between maze scores and a standardized measure of reading. In addition, t tests were conducted to compare fall to spring growth for each scoring procedure. Results indicated that scores derived from the different procedures are highly correlated, demonstrate criterion‐related validity, and show fall‐to‐spring growth. Educators working with struggling readers may use any of the five scoring procedures to obtain technically sound scores.

Full Author Index – Abstract Number (Bold number signifies first author)

The effects of electroconvulsive shock (ECS) on spatial memory first reported by Shavalia, Dodge, and Beatty (1981, Behavioral and Neural Biology, 31, 261–273) were systematically replicated in two experiments. Rats acquired concurrent spatial memories in two 8-arm radial mazes. Each rat was allowed four choices in Maze 1 and then, after 2 h, four choices in Maze 2. After 2 h each rat was tested for retention in Maze 1 and, after 2 more h, was tested for retention in Maze 2. A single ECS was administered immediately after the fourth choice in Maze 2. Retention (as measured by accuracy of Choices 5–8) was diminished for Maze 1 but not for Maze 2. In the second experiment, the delay between the retention tests was eliminated (thus holding the ECS—Choice 5 interval constant for the two mazes). Once again retention of Maze 1 was impaired and retention of Maze 2 was spared; that finding suggests that ECS does not proactively affect radial-arm maze performance. The results of a third experiment converge on the same conclusion; ECS failed to reduce levels of spontaneous alternation. Therefore, ECS appears to interfere retroactively with relatively old spatial memories and newly established memories appear to be immune to the amnestic effects of ECS. Implications and various explanations are considered.

Hippocampal infusions of apolipoprotein E peptides induce long-lasting cognitive impairment

The inheritance of the ɛ4 allele of apolipoprotein E (ApoE4) and cholinergic system dysfunction have long been associated with the pathology of Alzheimer's disease (AD). Recently, in vitro studies have established a direct link between ApoE and cholinergic function in that synthetic peptides containing segments of the ApoE protein (ApoE 133–149 and ApoE 141–148) interact with α7 nicotinic acetylcholine receptors (nAChRs) in the hippocampus. This raises the possibility that ApoE peptides may contribute to cognitive impairment in AD in that the hippocampus plays a key role in cognitive functioning. To test this, we acutely infused ApoE peptides into the ventral hippocampus of female Sprague–Dawley rats and assessed the resultant effects on radial-arm maze choice accuracy over a period of weeks after the infusion. Local ventral hippocampal infusion of ApoE peptides caused significant cognitive impairment in radial-arm maze learning that persisted several weeks after the acute infusion. This persisting deficit may be an important model for understanding the relationship between ApoE protein-induced neurotoxicity and cognitive impairment as well as serve as a platform for the development of new therapies to avoid neurotoxicity and cognitive decline.

Avoidance of tape-recorded milking facility noise by dairy heifers in a Y maze choice task

The effect of noise pre-recorded from a commercial milking facility on the choice behaviour of dairy heifers in a Y maze was examined. Sixteen animals were individually trained to associate noise onset with a particular maze arm and no noise (quiet) with the other maze arm. After a maze familiarisation period, each heifer was exposed to a mixture of training trials, where access to only one maze arm was made available, and choice trials, where both maze arms were available. In order to reduce possible interference from animals’ original side preferences or response patterns under two-alternative choice situations, training and choice trials were interspersed and the noise stimulus was presented in the maze arm first chosen after familiarisation. Over 11 exposures to the maze across 3 days, choice of maze arm (during choice trials), avoidance behaviour (time taken to enter maze arm, number of stops, handler intervention required) and heart rate (HR) were measured. Results showed that the percentage of heifers that chose the quiet arm changed significantly (p<0.01) from 31.3% to 81.3% over the course of the experiment. In addition, during training trials, animals took longer (p<0.05) to enter the maze arm, stopped more, required more handler intervention when entering and were more restless in the noise compared to the quiet arm. During training trials there was also a trend (p=0.06) indicating some increase in HR during noise trials compared to quiet trials. Overall, the results of this experiment indicate that milking facility noise is fear-provoking for dairy heifers and that they will learn to avoid this noise when given the opportunity. The experiment has also demonstrated successful use of this Y maze choice methodology for assessment of environmental stimuli in dairy heifers (previously Y maze methods have only been used to assess handling and husbandry practices in cattle).

Histamine H 1 receptor involvement in prepulse inhibition and memory function: Relevance for the antipsychotic actions of clozapine

Histamine H 1 blockade is one of the more prominent actions of the multi-receptor acting antipsychotic clozapine. It is currently not known how much this H 1 antagonism of clozapine contributes to the therapeutic or adverse side effects of clozapine. The current studies with Sprague-Dawley rats were conducted to determine the participation of histaminergic H 1 receptor subtype in sensorimotor plasticity and memory function affected by clozapine using tests of prepulse inhibition (PPI) and radial-arm maze choice accuracy. The PPI impairment caused by the glutamate antagonist dizocilpine (MK-801) was significantly attenuated by clozapine. In the current project, we found that the selective H 1 antagonist pyrilamine also reversed the dizocilpine-induced impairment in PPI of tactile startle with an auditory prepulse. In the radial-arm maze (RAM), pyrilamine, like clozapine, impaired working memory and caused a significant dose-related slowing of response. Pyrilamine, however, decreased the number of reference memory errors. We have previously shown that nicotine effectively attenuates the clozapine-induced working memory impairment, but in the current study, nicotine did not significantly alter the effects of pyrilamine on the RAM. In summary, the therapeutic effect of clozapine in reversing PPI impairment was mimicked by the H 1 antagonist pyrilamine, while pyrilamine had a mixed effect on cognition. Pyrilamine impaired working memory but improved reference memory in rats. Thus, H 1 antagonism seems to play a role in part of the beneficial actions of antipsychotics, such as clozapine.

Effects of clozapine on memory function in the rat neonatal hippocampal lesion model of schizophrenia

Clozapine is an effective atypical antipsychotic drug used to treat schizophrenia. It has the advantage of producing fewer extrapyramidal motor side effects than typical antipsychotic drugs such as haloperidol. Schizophrenia involves more than the hallmark symptom of psychosis. Substantial cognitive impairment is also seen. Effective drug treatments against the cognitive impairment of schizophrenia need to be developed. The current study was conducted to determine the effects of clozapine on working memory in the rat neonatal hippocampal lesion model of schizophrenia, which includes symptoms of cognitive impairment. Infant Sprague-Dawley rats were given ibotenic acid lesions of the hippocampus on day 7 of age (using the day of birth as day 0). Controls were given vehicle infusions. In adulthood, the rats were trained on the 8-arm radial maze using the win-shift procedure. After 6 sessions of training, the lesioned rats and their controls were administered repeated injections of saline or clozapine (2.5 mg/kg) for the next 12 sessions of training. The females had significant radial-arm maze choice accuracy impairments caused by either clozapine or the hippocampal lesion, but the combination of the two treatments had no additive effect. The males showed a different pattern of effects. Intact males did not show a significant clozapine-induced impairment, whereas males with hippocampal lesions did show significant clozapine-induced impairment although hippocampal lesions by themselves did not significantly impair male choice accuracy. These data show that clozapine can cause memory impairment and it potentiates rather than reverses hippocampal lesion-induced deficits. There are critical sex-related differences in these effects.

Nicotine–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.

Ventral hippocampal α4β2 nicotinic receptors and chronic nicotine effects on memory

Chronic nicotine administration has been repeatedly shown to facilitate working memory function in rats on the radial-arm maze. The critical neural mechanisms for this effect are still being discovered. The nicotinic nature of the chronic nicotine induced memory improvement is supported by the finding that it is blocked by chronic mecamylamine co-infusion. The hippocampus also appears to be critically important. Hippocampal ibotenic acid lesions block the effect. Within the hippocampus, we have found that the α4β2 nicotinic receptor subtype is involved in memory functioning. Acute ventral hippocampal infusions of the α4β2 nicotinic antagonist dihydro-β-erythroidine (DHβE) significantly decreased working memory performance in the radial-arm maze. The aim of the current study was to determine the importance of α4β2 receptors within the ventral hippocampus for the memory enhancing effects of chronic nicotine treatment. Adult female Sprague–Dawley rats were trained on the 8-arm radial maze and were cannulated bilaterally in the ventral hippocampus. Osmotic minipumps administering chronic nicotine at a rate of 5 mg per kg per day were also implanted in the nicotine treatment rats. Control rats received saline-only minipumps. For a period of 4 weeks after surgery, each rat received bilateral hippocampal infusions of 0, 2, 6 and 18 μg per side of DHβE and tested for memory performance on the radial-arm maze. Radial-arm maze choice accuracy was impaired by acute hippocampal DHβE infusion in a dose-related fashion. This acute hippocampal DHβE-induced choice accuracy impairment was eliminated by chronic systemic nicotine infusion. Chronic nicotine in combination with acute vehicle hippocampal infusion was not seen to alter choice accuracy. Response latency was not found to be altered by acute hippocampal DHβE in the absence of chronic nicotine administration, but it did attenuate the response latency reduction induced by chronic nicotine infusion. Wet dog shakes were not found to be affected by hippocampal DHβE when given without chronic nicotine. Wet dog shakes were significantly increased by chronic nicotine infusion. Intra-hippocampal DHβE significantly potentiated this effect. The results from the current study reinforce the hypothesis that ventral hippocampal α4β2 nicotinic receptors are important for memory function. These receptors may also have a role to play in the development of other aspects of behavior associated with chronic nicotine treatment.

Rapid neurobehavioral analysis of Pfiesteria piscicida effects in juvenile and adult rats

The estuarine dinoflagellate Pfiesteria piscicida is known to kill fish and has been associated with neurocognitive deficits in humans. We have developed a rat model to demonstrate that exposure to Pfiesteria causes significant learning impairments. This has been repeatedly seen as a choice accuracy impairment during radial-arm maze learning. Pfiesteria-induced effects were also seen in a locomotor activity test in the figure-8 apparatus. The current studies used the short-term radial-arm maze acquisition, the figure-8 activity test, and the functional observational battery (FOB) to assess Pfiesteria-induced neurobehavioral effects in adult and juvenile rats. In study 1, the neurobehavioral potency of three different Pfiesteria cultures (Pf 113, Pf 728, and Pf Vandermere) was assessed. Ninety-six (12 per group) adult female Sprague–Dawley rats were injected subcutaneously with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600 or 106,800 Pfiesteria cells per kilogram of rat body weight). One control group ( N = 12) was injected with saline and one ( N = 12) with aquarium water not containing Pfiesteria. All three of the Pfiesteria samples ( p < 0.05) impaired choice accuracy over the first six sessions of training. At the time of the radial-arm maze choice accuracy impairment, no overt Pfiesteria-related effects were seen using an FOB, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the figure-8 apparatus, Pfiesteria treatment caused a significant decrease in mean locomotor activity. In study 2, the neurobehavioral effects of the Pf 728 sample type were assessed in juvenile rats. Twenty-four day-old male and female rats were injected with 35,600 or 106,800 Pf-728 Pfiesteria cells per kilogram of rat body weight. As with adult females, the juvenile rats showed a significant impairment in radial-arm maze choice accuracy. No changes in locomotor activity or the FOB were detected in the juvenile rats. Furthermore, there were no differences between male and female rats in the Pfiesteria-induced choice accuracy impairment. Pfiesteria effects on choice accuracy in the radial-arm maze in rats constitute a critical component of the model of Pfiesteria toxicity, because the hallmark of Pfiesteria toxicity in humans is cognitive dysfunction. Our finding that analysis of the first six sessions of radial-arm maze testing is sufficient for determining the effect means that this test will be useful as a rapid screen for identifying the critical neurotoxin(s) of Pfiesteria in future studies.

Ventral hippocampal dopamine D 1 and D 2 systems and spatial working memory in rats

The hippocampus has long been known to be important for memory function. However, the involvement of hippocampal dopamine systems with memory has received little attention. In the current study, dopamine D 1 and D 2 hippocampal receptor system involvement with memory was assessed in female Sprague–Dawley rats by local infusion of D 1 and D 2 agonists and antagonists into the ventral hippocampus. Working memory performance was assessed on the radial-arm maze. Neither the D 1 agonist dihydrexidine (1.1–10 μg/side) nor the D 1 antagonist SCH 23390 (0.19–1.67 μg/side) was effective in significantly altering radial-arm maze choice accuracy. In contrast, there were significant and opposite effects of D 2 agonist and antagonist treatments. The D 2 agonist quinpirole caused a significant ( P<0.05) dose-related improvement in choice accuracy over a dose range of 1.1–10 μg/side. In a complementary fashion, the D 2 antagonist raclopride caused a significant ( P<0.05) dose-related choice accuracy deficit over a range of 0.19–1.67 μg/side. This study provides clear evidence that hippocampal D 2 activity is positively related to working memory performance, while evidence for D 1 systems is less compelling. Dopamine D 2 receptors in the ventral hippocampus were shown to have important influences on spatial working memory. In a consistent pattern of effects ventral hippocampal infusion of the D 2 agonist quinpirole improved working memory performance in the radial-arm maze, while ventral hippocampal infusion of the D 2 antagonist raclopride impaired performance.

Nicotinic antagonist administration into the ventral hippocampus and spatial working memory in rats

Nicotinic acetylcholine receptors are important for maintaining optimal memory performance. In order to more fully characterize the involvement of nicotinic systems in memory, the contributions of nicotinic acetylcholine receptor subtypes were investigated. This study targeted the α7 and α4 β2 nicotinic receptors in the ventral hippocampus, an area known to be important for spatial working memory. Antagonists of α7 and α4 β2 receptors were locally infused into the ventral hippocampus of rats and the effects on memory were examined with the radial-arm maze. The subtype-specific competitive antagonists infused into separate groups of rats were methyllycaconitine citrate (an α7 antagonist) and dihydro- β-erythroidine hydrobromide (an α4 β2 antagonist). Their effects on radial-arm maze performance were contrasted with the non-specific competitive antagonist, d-tubocurarine chloride. Significant deficits in radial-arm maze choice accuracy performance were found at 78.7 μg/side for methyllycaconitine and at 106.9 μg/side for dihydro- β-erythroidine. Increased response latency was also seen at these doses. Tubocurarine induced seizures at doses previously reported to have no effect. Wet dog shakes were seen in most rats at 0.1 μg/side with tubocurarine, 26.3 μg/side with methyllycaconitine and 106.9 μg/side with dihydro- β-erythroidine. This study suggests that both α7 and α4 β2 nicotinic acetylcholine receptor subtypes are involved in working memory formation and that the hippocampus is a critical site for nicotinic cholinergic involvement in memory function, though the high doses of antagonists needed to produce the memory impairment may have had less than completely specific effects.

Cognitive effects of neonatal hippocampal lesions in a rat model of schizophrenia

Lesioning the ventral hippocampus of neonatal rats has been proposed as an experimental model of schizophrenia. This lesion causes a syndrome of hyperresponsivity to the stimulant effects of amphetamine, impaired grooming and disrupted social interactions, effects that emerge during adolescence, much like schizophrenia. Persisting cognitive effects of neonatal ventral hippocampal lesions were assessed in the current study, because the hippocampus is critically important for a variety of cognitive functions and cognitive impairment and because it is an important feature of schizophrenia. Spatial learning and working memory were assessed in the radial-arm maze, which is sensitive to the adverse effects of hippocampal lesions made in adults. Lesioned rats showed pronounced deficits in radial-arm maze choice accuracy that persisted throughout training. Deficits were seen during the prepubertal period as well as in adulthood. Even though the lesioned rats performed more poorly, they were significantly less sensitive to the amnestic effects of the nicotinic antagonist mecamylamine and the muscarinic antagonist scopolamine. No significant effects of nicotine or amphetamine were seen in either the lesioned or control groups. The long-lasting deficits in spatial learning and working memory resulting from neonatal ventral hippocampal lesions show that, unlike frontal cortical lesions during the same age, the effects of hippocampal lesions are not overcome during development. The resistance to the amnestic effects of nicotinic and muscarinic acetylcholine (ACh) antagonists suggests that the hippocampus is a critical site for the action of these drugs. Neonatal hippocampal lesions may provide a good model of the cognitive impairments of schizophrenia and may be useful to assess novel drug effects to counteract the cognitive deficits in schizophrenia.

Pergolide interactions with nicotine and pilocarpine in rats on the radial-arm maze

Antagonists of nicotinic and muscarinic acetylcholinergic (ACh) receptors have significant interactions with dopaminergic (DA) ligands with regard to radial-arm maze choice accuracy. The current studies examined the interactions of agonists of nicotinic and muscarinic ACh receptors with the DA agonist pergolide. Pergolide given in a range from 0.03–1.0 mg/kg had no detectable effect on radial-arm maze choice accuracy when given alone. With this dose range there was a linear increase in response latency. Pergolide had significant interactive effects with the nicotinic and muscarinic agonists nicotine and pilocarpine. Given together with nicotine, pergolide produced a significantly elevated linear increase in accuracy relative to when it was given alone. With pilocarpine, pergolide had an inverted U-shaped effect improving choice accuracy at low to moderate doses of 0.03 and 0.1 mg/kg. These results support previous findings of DAACh interactions with regard to radial-arm maze choice accuracy. Combined DA-ACh treatment may be a useful treatment of cognitive dysfunction.

Acute and chronic nicotinic interactions with dopamine systems and working memory performance.

Nicotine has been found to improve memory performance in a variety of tests in rats, monkeys, and humans. Interactions of nicotinic systems with dopamine (DA) systems may be important for this effect. We conducted a series of studies of nicotinic agonist and antagonist interactions with DA systems using rats in a win-shift working memory task in the radial-arm maze. The working memory deficit caused by the nicotinic antagonist mecamylamine was potentiated by the D1/D2 DA antagonist haloperidol and the specific D2 antagonist raclopride. In contrast, the mecamylamine-induced deficit was reversed by co-administration of the D2/D3 agonist quinpirole. Nicotine also has significant interactions with dopamine drugs with regard to working memory performance in the radial-arm maze. The DA agonist pergolide did not by itself improve radial-arm maze memory performance, but when given together with nicotine it produced an elevated dose-dependent increase in choice accuracy. The D1 agonist SKF 38393 significantly impaired radial-arm maze choice accuracy. Nicotine was effective in reversing this deficit. When given together with nicotine, the D2/D3 agonist quinpirole improved RAM choice accuracy relative to either drug alone. Acute local infusion of mecamylamine to the midbrain DA nuclei effectively impairs working memory function in the radial-arm maze. In contrast to acute nicotinic manipulations, considerably less evidence exists that the effects of chronic nicotine administration are influenced by DA systems. This may be an example of the different neural substrates that underlie the memory improvement caused by acute and chronic nicotine.

Dopaminergic drugs reverse the impairment of radial-arm maze performance caused by lesions involving the cholinergic medial pathway

Pharmacological studies have shown that both cholinergic and dopaminergic transmitter systems are crucial for optimal choice accuracy in the radial-arm maze and that these systems interact in a complex fashion. Lesion studies have provided evidence that the basal nuclear complex of the forebrain, the origin of cholinergic projections to the cerebral mantle, may be critical for the cholinergic modulation of learning and memory. We have shown that knife-cut lesions of the medial cholinergic pathway significantly impair radial-arm maze choice accuracy performance. The current study examined the effectiveness of D 1 and D 2 ligands in counteracting this lesion-induced deficit. The adverse effects of medial cholinergic pathway lesions were diminished or reversed by daily treatment with a D 1 agonist (SKF 38393), a D 2 agonist (LY 171555) or a D 1 antagonist (SCH 23390), but were not affected by treatment with a D 2 antagonist (raclopride). The three beneficial treatments have previously been found to attenuate the adverse effects of nictonic or muscarinic blockade on choice accuracy performance in the radial-arm maze. The finding that these dopaminergic drugs ameliorate the memory deficit caused by lesions involving the cholinergic medial pathway suggests the importance of interactions between cholinergic and dopaminergic systems in radial-arm maze performance. These results may provide leads for the development of novel therapeutic approaches for treating human disorders thought to result from cholinergic hypofunction.

Does a cognitive map guide choices in the radial-arm maze?

Fifteen rats performed in a standard radial-arm maze task (Experiment 1) and in a modified task with a set of forced choices and a 15-min retention interval prior to completion of the maze (Experiment 2). In addition to the standard measure of choice in the radial-arm maze, orientation toward arms was measured and considered to constitute go-no-go "microchoice" decisions. Rats investigated but rejected many arms. A model of choice was developed in which it was assumed that choice decisions about arms were made independently and that microchoices were not selectively guided toward baited arms. The model performed nearly as well as the rats. These results place important limitations on the theory that choice behavior in the radial-arm maze is guided by a cognitive map.