Radial-arm Maze Performance In Rats Research Articles

Intrahippocampal d-cycloserine improves MK-801-induced memory deficits: radial-arm maze performance in rats

In order to investigate whether strychnine-insensitive glycine sites coupled with hippocampal NMDA ( N-methyl- d-aspartate) receptors are involved in spatial memory in rats, we examined the effects of intrahippocampal treatment of d-cycloserine (DCS), a glycine-site agonist, on spatial-memory deficits which were produced by an NMDA antagonist MK-801 (dizocilpine) on the radial-arm maze task. After the acquisition of this task, the radial-maze performance was tested under the combined treatments of intraperitoneal MK-801 or saline (SAL) and intrahippocampal DCS or SAL. The results showed that MK-801 impaired the performance, and that DCS improved the MK-801-induced performance impairment. These results suggest that glycine sites are involved in spatial memory through their modulatory action on hippocampal NMDA receptors.

Effects of intrahippocampal AP5 treatment on radial-arm maze performance in rats

The purpose of the present study was to investigate the possible involvement of hippocampal NMDA ( N-methyl- d-aspartate) receptors in spatial memory in rats by means of intrahippocampal injection of an NMDA antagonist, AP5 ( d, l-2-amino-5-phosphonopentanoic acid). In Expt. 1, spontaneous motor activity (locomotor activity and rearing) was measured in an open-field after bilateral AP5 injection into the hippocampus, and it was shown that AP5 did not affect general activities within the dosage used in the present study. In Expt. 2, radial-maze performance was observed after the intrahippocampal injection of AP5. Rats were required to consume all the pellets which were put on each of the eight arms of the maze without revisiting the arms. AP5 produced dose-dependent impairment on the choice performance in the radial-arm maze, but did not have any effect on their running time. These results suggest that hippocampal NMDA receptors are involved in spatial memory.

Chronic Haloperidol Administration Does Not Block Acute Nicotine-Induced Improvements in Radial-Arm Maze Performance in the Rat

Nicotine has been found to improve cognitive performance in a variety of tasks including the radial maze. Nicotine has also been shown to promote the release of a variety of neurotransmitters including dopamine (DA). DA has been found to be important for nicotine’s reinforcing effects. DA involvement with nicotine’s cognitive effects is unclear. In the current study, the effects of acute nicotine injections (0, 0.1, 0.2, or 0.4 mg/kg) were examined on radial-arm maze performance in rats given chronic infusions the DA antagonist haloperidol (0, 0.2, or 0.6 mg/kg/day). Chronic haloperidol infusion was not found to attenuate the memory improvement caused by acute nicotine injection. In fact, the dose-related nicotine-induced memory improvement was clearer in the haloperidol-treated groups than in controls. This is similar to the effect of nicotine we saw in human subjects given chronic doses of haloperidol. Our previous studies demonstrated significant nicotinic–DA interactions with regard to memory function. The current results suggest that in the DA–nicotinic relationship DA stimulation is not necessary for the memory improvement caused by nicotine.

Differential behavioral effects of supracallosal and infracallosal lesions of the septohippocampal pathways: No ameliorative effects of oxotremorine or pilocarpine on radial-maze performance

We examined the effects in young adult female Long-Evans rats of single or combined lesions of the infracallosal and supracallosal septohippocampal pathways on a battery of behavioral tasks over two postoperative periods (14-65 and 75-150 days, respectively). During the first period, rats with lesions of the infracallosal pathways, whether given alone or in combination with lesions of the supracallosal pathways, were more active in the open field and in their home cage, and showed increased reactivity to novel extracage stimuli. Behavioral results during the second postoperative period were similar to those of the first except that rats with lesions of the infracallosal pathways (either alone or in combination with lesions of the supracallosal pathways) were no longer hyperactive in their home cage and rats with the infracallosal lesion alone were no longer hyperactive in the open field. We also observed in rats with lesions of the infracallosal pathways impaired performance in the radial-arm maze task, whether conducted under an uninterrupted protocol (first and second postoperative periods) or with a 1-min intratrial interruption (second postoperative period). Thus, behavioral deficits were observed only in rats with a lesion to the infracallosal component of the septohippocampal pathways, the behavior of rats with the combined lesions being similar to that of rats with single lesions of the infracallosal pathways in most measures. The behavior of rats with lesions of the supracallosal pathways did not differ from that of sham-operated controls in any measure at either postoperative period. Acute, systemic injections of oxotremorine (0.03 or 0.1 mg/kg, ip) or pilocarpine (0.32 or 1.0 mg/kg, ip), two muscarinic agonists, did not affect radial-arm maze performance under either the uninterrupted or interrupted protocol. The use of nonspecific muscarinic agonists does not appear to be sufficient to enhance radial-arm maze performance in rats with infracallosal septohippocampal lesions which, in contrast to supracallosal lesions, were shown to induce a deficit in this task.

The effects of prenatal nicotine on radial-arm maze performance in rats

Studies have revealed lasting cognitive impairments, including deficits in attention and learning, in the offspring of women who smoke. Animal models have shown that prenatal nicotine can induce behavioral impairments, including deficits in learning and memory, and one study showed that only females were impaired on a maze task. The purpose of the present experiment was two-fold: 1) to attempt to replicate the reported sex difference in maze learning and 2) to assess the ability of nicotine-treated subjects to learn a maze that placed particularly heavy demands on their attentional capabilities. Pregnant mothers were given 6.0 mg/kg/day of nicotine in their drinking water. Offspring of both sexes were tested following weaning in an 8-arm-radial maze using a confinement procedure. Results showed that prenatal nicotine treatment produced significant impairments in performance in the radial-arm maze. These impairments were seen in animals of both sexes, a finding which challenges the view that only females prenatally treated with nicotine show deficits in maze learning.

Impairment of radial-arm maze performance in rats following lesions involving the cholinergic medial pathway: Reversal by arecoline and differential effects of muscarinic and nicotinic antagonists

Pharmacologic studies have indicated that accurate performance on the radial-arm maze depends upon the integrity of both nicotinic and muscarinic cholinergic neurotransmitter systems and that these systems interact in a complex fashion. Although numerous studies have suggested that pathways deriving from the basal nuclear complex of the forebrain are critical for the cholinergic modulation of learning and memory, most have focussed on the septohippocampal projection, and none have specifically targeted the medial or lateral systems. In Experiment 1, cortical knife cuts interrupting the medial cholinergic pathway were made at the level of the caudate-putamen nucleus. Such transections produced a robust but temporary disruption of choice accuracy performance in the radial-arm maze. Recovery of this behavior occurred within 10 days and before cholinergic fiber regeneration, suggesting that compensatory changes could have taken place in non-ablated neuronal circuits. In Experiment 2, daily postsurgical administration of arecoline, an agonist with predominantly muscarinic actions, was found to virtually eliminate the adverse behavioral effects of medial pathway transections, indicating that the deficit could be attributable, in part, to disruption of cholinergic projections. In Experiment 3, the effects of scopolamine, a muscarinic antagonist, and mecamylamine, a nicotinic antagonist, were examined in rats with medial cholinergic pathway transections after behavior had returned postsurgically to control levels. Although both drugs attenuated radial-arm maze performance before knife cuts, only scopolamine reduced choice accuracy following surgery. We conclude that the medial cholinergic pathway, particularly its nicotinic actions, plays an important role in cognitive function, at least as exemplified by radial-arm maze performance. Muscarinic mechanisms associated with other telencephalically projecting cholinergic networks, as well as possibly with the medial pathway itself, appear to operate interactively with nicotinic influences.

O-350 - Effects of scopolamine upon delayed radial-arm maze performance in rats.

O-350 - Effects of scopolamine upon delayed radial-arm maze performance in rats.

Chronic nicotine and withdrawal effects on radial-arm maze performance in rats

Rats were tested for choice accuracy in an eight-arm radial maze during and after chronic administration of nicotine via subcutaneously implanted glass and Silastic capsules. Nicotine administration significantly improved choice accuracy relative to controls. The effect gradually became apparent over the first 2 weeks of exposure and persisted through the third week. Surprisingly, the significant facilitation of the nicotine-treated rats relative to controls continued for 2 weeks after the end of nicotine administration. No effects of nicotine were seen on choice latency or the strategy to make adjacent arm entries.

Anticholinergic sensitivity following chronic nicotine administration as measured by radial-arm maze performance in rats

Chronic nicotine administration in rats has been previously found to improve choice accuracy performance of rats in the radial-arm maze. A nicotine-induced choice accuracy improvement was also seen in the current study. Rats were trained to asymptotic levels of choice accuracy performance on a working memory paradigm in an 8-arm radial maze. During and after 3 weeks of chronic nicotine treatment, rats were tested for sensitivity to acute doses of the nicotinic and muscarinic receptor antagonists, mecamylamine and scopolamine. During the first week of administration, nicotine-treated rats were supersensitive to the sedation caused by mecamylamine. This suggests that nicotine may not have been acting as a simple nicotinic agonist, since in this case, the opposite effect, an attenuated effect of mecamylamine in the nicotine-treated group, would have been expected. Three to 4 weeks after withdrawal from chronic nicotine administration, the treated rats were more sensitive to the choice accuracy deficits caused by the muscarinic blocker scopolamine (0.16 mg/kg) and the nicotinic blocker mecamylamine (10 mg/kg). This supersensitivity may have been due to a lasting change caused by chronic nicotine in the cholinergic bases of memory function.

Radial-arm maze performance in rats is impaired by a combination of nicotinic-cholinergic and D2 dopaminergic antagonist drugs.

Performance on the radial-arm maze depends on the integrity of both cholinergic and dopaminergic systems. We have previously found that administration of either the nicotinic-cholinergic antagonist, mecamylamine, or the muscarinic-cholinergic antagonist, scopolamine, impairs choice accuracy in the radial-arm maze. Co-administration of the dopaminergic antagonist, haloperidol, ameliorated the performance deficit caused by scopolamine but exacerbated the deficit caused by mecamylamine. Furthermore, antagonism of the effect of scopolamine is due specifically to blockade of D1 receptors. In the present experiment behaviorally subthreshold doses of mecamylamine and the D2 antagonist raclopride impaired maze performance when administered together. No interactive effects were observed between mecamylamine and the D1 antagonist SCH 23390. Although several of the drug treatments studied significantly increased choice latency, an index of motor behavior, there was no perfect relationship between choice accuracy and choice latency. These data indicate that nicotinic-cholinergic and muscarinic-cholinergic systems interact selectively and differentially with D1 and D2 dopaminergic systems.

Nicotinic—dopaminergic relationships and radial-arm maze performance in rats

Accurate performance on the radial-arm maze is dependent upon the integrity of nicotinic-cholinergic, muscarinic-cholinergic, and dopaminergic systems. Pharmacological blockade of these systems with mecamylamine, scopolamine, or haloperidol impairs choice accuracy in the maze. We have previously demonstrated that the performance deficit caused by muscarinic blockade is enhanced by coadministration of the nicotinic antagonist, mecamylamine, and is diminished by coadministration of the dopamine antagonist, haloperidol. In the present study, it was found that the choice accuracy deficit produced by nicotinic blockade is enhanced, not antagonized, by coadministration of haloperidol. Thus, although both nicotinic and muscarinic cholinergic systems are involved in radial-arm maze performance and antagonists of these receptors are additive in the deficits they cause, nicotinic and muscarinic interactions with dopaminergic systems are opposite in nature.

Scopolamine interactions with D1 and D2 antagonists on radial-arm maze performance in rats

Recent evidence indicates that acetylcholine and dopamine play complementary roles in cognitive as well as motor functions. In our previous study, the dopamine receptor blocker, haloperidol, was found to attenuate the radial-arm maze choice accuracy deficit caused by the muscarinic acetylcholine receptor blocker, scopolamine. Haloperidol has activity in blocking both D1 and D2 dopamine receptor subtypes. The current study was conducted to determine whether this dopamine-acetylcholine interaction specifically involved D1 or D2 dopamine receptors. The D1 antagonist, SCH 23390, and the D2 antagonist, raclopride, were administered with a dose of scopolamine which caused choice accuracy deficits in the radial-arm maze. The scopolamine-induced deficit was reversed by SCH 23390, the D1 antagonist, indicating that D1 blockade alone is sufficient to reverse the amnestic effects of muscarinic blockade. There was no indication in this study that the D2 blocker, raclopride, had a similar effect. However, this does not mean that such an effect may not be present at other doses of raclopride or with other D2 antagonists. The present finding that D1 blockade counteracts scopolamine-induced cognitive dysfunction not only furthers the understanding of dopamine-acetylcholine relationships in cognitive function, it also suggests a promising direction for the development of treatments for cognitive dysfunction due to cholinergic loss.

Effects of the nicotinic receptor blocker mecamylamine on radial-arm maze performance in rats

Lesions of cholinergic neurons have been found by many investigators to impair choice accuracy in the radial arm maze. Because muscarinic receptor blockers, such as scopolamine, have also repeatedly been found to impair choice accuracy in the radial-arm maze, it has generally been thought that the critical effect of cholinergic lesions is the deafferentation of muscarinic receptors. The possible involvement of nicotinic receptors in the cholinergic bases of cognitive performance in the radial-arm maze has not been as well investigated. The present study examined the effects of the blockade of nicotinic receptors on performance of female Sprague-Dawley rats in the radial-arm maze. Acute administration of the the nicotinic receptor blocker, mecamylamine (10 mg/kg) was found to significantly impair radial-arm maze choice accuracy. This dose also caused a significant increase in response latency in the maze. The effect on choice behavior but not locomotor speed seemed to be due to the central effects of mecamylamine, because administration of the peripheral nicotine receptor blocker, hexamethonium (20 mg/kg), did not impair choice accuracy, even though it did increase response latency to a similar degree as the 10-mg/kg dose of mecamylamine. Lower doses of mecamylamine (2.5 and 5 mg/kg) did not impair choice accuracy. These results indicate that central nicotinic as well as muscarinic cholinergic receptors are involved with cognitive functioning.

Chronic haloperidol effects on oral movements and radial-arm maze performance in rats

Rats were examined for were examined for the development of adverse motor and cognitive effects during and after 24 weeks of chronic haloperidol (HAL) administration using an 8-arm maze and a computerized apparatus for measuring spontaneous oral movements. In the maze, HAL caused a significant decline in choice accuracy only during the first week of administration, whereas it caused a significant decline in locomotor speed throughout drug administration. There were no effects of HAL on maze behavior after withdrawal. Haloperidol reduced the number of mouth movements during drug administration, but after withdrawal there was a significant increase. This replicated a previous finding from our lab. The oral movements which did occur in the HAL-treated rats were slower than normal. The timing of the HAL-induced cognitive dysfunction was similar to the Parkinson-like disorder shown by patients given chronic neuroleptics, whereas the timing of the increase in oral movements after the withdrawal of HAL was more related to the appearance of tardive dyskinesia. There was evidence in both tests of a persisting sedation during chronic neuroleptic administration.

Release from proactive interference by experimental amnesia: electroconvulsive shock improves radial-arm maze performance in rats

Rats were trained in an eight-arm radial maze and tested using a proactive interference (PI) procedure. Each test trial consisted of forced choices of four randomly selected arms followed, after a 2-h delay, by free choices among all eight arms. Normally, rats chose correctly during the free choices by entering and retrieving food from the four arms not yet visited during the test trial. Occasionally, an interference trial preceded the test trial by 1.5 or 3 h; interference trials consisted of forced choices of another four arms and an immediate test. The presence of an interference trial lowered test-trial performance (PI). Electroconvulsive shock (ECS) administered immediately after the interference trial had no effect; i.e., PI was still observed. When ECS was administered at the midpoint of the 3-h intertrial interval, performance increased to control (no ECS, no PI) levels. Such release from PI, however, was not obtained, and test-trial performance remained inaccurate when ECS was delivered immediately after the forced choices of the test trial (either 1.5 or 3 h after the interference trial).

Behavioral perturbations in the vitamin K-deficient rat

Anecdotal observations of the behavior of rats with a vitamin K-deficiency suggested that this deficiency was associated with hypoactivity, general malaise, and a lack of exploratory behavior. These observations were pursued by assessing locomotor activity in a circular photocell-monitored track, open-field activity, and radial-arm maze performance in rats rendered vitamin K-deficient by dietary depletion or by warfarin treatment. There was a significant reduction (approximately 25% at the median) in the locomotor activity of dietary vitamin K-deficient rats compared with rats fed a control diet. In the open-field, warfarin administration was associated with a significant shift from more exploratory behaviors to less exploratory behaviors. Consistent with these findings, radial-arm maze assessment showed a comparative reduction in locomotor activity in the dietary vitamin K-deficient rats with no alteration in performance, i.e., short-term memory. These animal behavioral studies suggest that sub-clinical and clinical vitamin K-deficiency may contribute to physical and psychiatric symptomatology.