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Biomedical subjects

O Buresová

Publications and source records attributed to O Buresová.

At least 19 recordsLinked to original sources

Can rats solve a simple version of the traveling salesman problem?

Whereas correct tours through the radial arm maze are almost equally long, free choice mazes with multiple goals scattered in an open field allow the animal to select the shortest one from a multitude of correct tours. Thirteen rats were trained (at 10 trials per day) to visit an array of cylindrical feeders in an open field (40 x 100 cm) with reward available only when visiting the last feeder of the set. In Expt. 1 with eight feeders arranged in five different configurations the rats made after 10 days of training 1 error in the first 8 choices and incidence of errorless trials was about 20%. In Expt. 2. the use of six feeders in a rectangular (A) or double triangle (B) configuration increased the incidence of errorless trials to 60%. Expt. 3 showed that performance in the 6-feeder maze was significantly impaired by 6 mg/kg ketamine or 0.25 mg/kg scopolamine but not by lower dosages of these drugs. Tours generated on errorless trials (each feeder visited only once) during 10 days of Expt. 2 were analyzed. Six places can be visited in 6! = 720 different closed tours the lengths of which (in arbitrary units) range from 6.00 to 10.12 for A and from 6.83 to 10.47 for B. Whereas random generation of correct routes yielded only 5% of the shortest tours, they were clearly preferred by rats (41% in A and 45% in B). The apparent proficiency of rats in this optimization problem is probably not due to cognitive comparison of the possible correct routes but rather to following a simple rule 'Always go to the nearest not yet visited feeder'.

Animals

Brain transplants enhance rather than reduce the impairment of spatial memory and olfaction in bulbectomized rats.

The possibility to compensate the loss of olfactory and non-olfactory functions due to removal of the olfactory bulb by embryonal brain grafts was investigated in adult rats. Spatial working memory was examined in an 8-arm radial water maze task 6 weeks after bulbectomy. During 15 daily trials, performance gradually improved in bulbectomized controls (n = 10) and in rats with olfactory bulb transplants (n = 9), but did not attain that of intact controls (n = 10). No improvement was observed in the rats with substantia nigra grafts (n = 8). Eleven weeks after bulbectomy, the same rats were tested in the water tank navigation task. The performance improved during ten 12-trial sessions in bulbectomized rats less than in intact controls, but more than in the transplanted rats. The olfactory food retrieval test performed 14 weeks after bulbectomy revealed almost full recovery of smell in bulbectomized rats, but not in the transplanted animals. It is concluded that the spatial memory deficit is probably due to bulbectomy-induced interference with septohippocampal function which is not alleviated, but rather enhanced by transplantation. The results suggest that the effect of brain grafting is not always beneficial.

Animals

Conditioned taste aversion elicited by intracerebral administration of drugs.

Conditioned taste aversion (CTA) is a vital adaptive reaction governed by highly reliable but poorly understood central mechanisms. In an attempt to elucidate the site of action of various CTA eliciting drugs, equipotent dosages were applied by the systemic (i.p.) and intracerebral (i.c.) route. Rats were offered water on days 1 and 2. On day 3 they received 0.1% sodium saccharin (CS) followed by pentobarbital anaesthesia and i.p. or i.c. injection of the drug (US). After water on day 4, the rats were allowed to choose between water and saccharin on day 5. The putative central action of amphetamine was not confirmed by this experimental arrangement, since CTA was evoked by only moderately (about 10 times) lower i.c. than i.p. dosages. Similar ratio of the i.c. to i.p. effective dosages was obtained with carbachol. On the other hand, CTA of clearly central origin was caused by harmaline and by other monoamine oxidase inhibitors, pargyline and clorgyline, which elicited comparable aversion using 500, 400 and 250 times lower i.c. than i.p. dosages, respectively. The intracerebral gradient of the effect pointed to the lower medulla (inferior olive, raphe nuclei) as the critical brain region and to serotonin as the transmitter participating in the aversive labeling of the gustatory stimulus. The CTA-forming mechanism can also be studied by analysing the action of drugs, e.g. convulsants, which do not produce CTA even when applied at highly toxic dosages (LD 50) eliciting long lasting convulsions (picrotoxin, 5 mg/kg; bicuculline, 5 mg/kg). It is concluded that comparison of brain events elicited by drugs which can or cannot serve as unconditioned stimuli in the CTA paradigm may substantially contribute to the exploration of the underlying neural mechanisms.

Animals

Differential effect of prior paradoxical sleep deprivation on conditioned taste aversion, neophobia and attenuation of neophobia to solid food in rats.

The effect of paradoxical sleep deprivation (PSD) on subsequent acquisition of conditioned taste aversion (CTA) to liquid diets is confounded by the uncertain level of thirst when using the water tank procedure. This difficulty is eliminated when examining CTA and attenuation of neophobia (AN) to solid diets. Adult male rats (n = 100) were habituated to receive their daily ration of food during a 30-min stay in a box equipped with a row of 10 feeders baited with 2-3 g pieces of moist standard diet. 24-h PSD increased neophobic rejection of novel sweet food (with added 5% saccharose), but did not influence intensity of CTA elicited by LiCl poisoning. Addition of a bitter tasting red food dye to the sweet food caused marked neophobia which was enhanced by preceding PSD. Association of this unpalatable food with LiCl elicited strong CTA which extinguished faster in the PSD-pretreated animals. On the other hand, preacquisition PSD did not influence AN to the same stimulus. Sweet food with added blue dye elicited only mild neophobia which was enhanced by preceding 24-h PSD. Preacquisition PSD did not influence AN but significantly increased CTA to blue sweet food. It is concluded that PSD can either enhance or weaken CTA and that this complex effect on food selection learning cannot be explained by PSD-induced reduction of fear.

Animals

Does nondirectional signalization of target distance contribute to navigation in the Morris water maze?

The possibility that rats can navigate in the Morris water maze by reducing the difference between the memorized platform scene and the current sensory input was tested in nine blind rats. A computerized videosystem monitored the rats' movements in the pool and converted the rat-target distance into tones the frequency of which increased in 64 equal steps from 120 Hz at 128 cm to 7680 Hz at 0 cm. During 15 days of training to find a fixed platform position from different starting points (12 trials per day) average escape latencies decreased from 39.0 to 25.4 s. The performance significantly deteriorated when the acoustic distance signalization was omitted and/or when the target position was changed form trial to trial. It is concluded that blind rats solved the task by simultaneously employing search strategy based on position responses, mapping using acoustic background beacons, and distance reduction navigation. It is argued that the various strategies are additive and that their relative significance depends of the conditions of the experiment.

Acoustic Stimulation

Conditioned taste aversion induced in rats by intracerebral or systemic administration of monoamine oxidase inhibitors.

Conditioned taste aversion (CTA) elicited by systemic or intracerebral application of the monoamine oxidase inhibitors clorgyline (C), pargyline (P) or deprenyl (D) was studied in 402 rats. Water-deprived animals were allowed 15 min access to 0.1% sodium saccharin (CS) followed 10 min later by IP or by intracerebral injection of the drug. In the latter case, the animals were anesthetized 5 min after saccharin drinking with pentobarbital and the drug was stereotaxically injected (1 microliter/min, 1-2 microliters) into the target structure. CTA was assessed in a two-choice retention test performed 2 days later. A geometric progression of three to six dosages applied to groups of rats (n = 10) was employed to establish the effective doses of the drugs which were 4, 20 and 32 mg/kg with IP and 2.5, 10 and 80 micrograms per rat with intracerebral (n. raphé magnus) injections of C, P, and D, respectively. The ratios of intracerebral to systemic dosages eliciting comparable CTA were 1:300 for C, 1:800 for P and 1:100 for D. Injections of 2.5 micrograms C and 10 micrograms P into the mesencephalic reticular formation, medial hypothalamus and cerebral cortex were ineffective, as were injections of 10 micrograms P into the nucleus of the solitary tract and cerebellum. The results indicate that CTA is elicited more efficiently by inhibition of monoamine oxidase A (selectively inhibited by C) than of monoamine oxidase B (selectively inhibited by D).

Animals

Differential effects of cholinergic blockade on performance of rats in the water tank navigation task and in a radial water maze.

The disruptive effect of cholinergic blockade was tested under conditions in which either the working memory or the spatial mapping requirements of the behavioral task were emphasized. In Experiment 1, 13 rats were trained in an eight-arm radial water maze to asymptotic performance. When delays of 5, 10, 20, and 40 min were inserted between Choice 4 and Choice 5, incidence of errors in Choices 5-8 increased after pretrial (20 min) scopolamine injection (0.2 mg/kg, ip) faster than under control conditions and approached chance level with the 40-min delay. Scopolamine after Choice 4 or pretrial methylscopolamine was ineffective. In Experiment 2, 30 rats were trained in a Morris water tank. Acquisition was impaired by pretrial injection (20 min) of 0.1 and 0.2 mg/kg scopolamine, but a higher dose (1.0 mg/kg) was required to impair overtrained performance. In a working memory version of the navigation task, scopolamine administered 20 min before the first trial deteriorated retention tested 40 min later at a dose of 1.0 but not at 0.4 and 0.2 mg/kg. It is concluded that the disruptive effect of scopolamine is proportional to the demands on the working memory component of the task whereas the use of an overtrained mapping strategy is relatively resistant to cholinergic blockade.

Animals

The effect of binocular and monocular viewing conditions on performance of rats in the Morris water maze.

The visually guided behaviour in the Morris water maze (using distal extramaze cues for navigation to a small invisible platform in a large pool of opaque water) was analyzed by comparing monocular and binocular performance of hooded rats in various versions of this task. A dish-shaped metal foil occluder connected to a carrier fixed to the frontal bones was used to restrict vision to one eye. Acquisition of the water maze task with one eye occluded proceeded at the same rate as with both eyes open. There was no difference in the transfer from binocular to monocular and from monocular to binocular viewing. Retrieval of the monocularly acquired habit was equally efficient with the same as with the contralateral eye. Similar results were obtained in naive and overtrained rats. In the working memory version of the task, rats received a single acquisition trial with a new position of the escape platform followed after a delay of 2, 5, 20 or 40 min by a single retrieval trial. Performance deteriorated with increasing delay faster under interocular transfer conditions then when the same eye was used in both trials. No signs of ocular dominance were found in this task. It is concluded that successful place learning is little affected by monocular or binocular viewing conditions, but that monocular impairment becomes apparent when the difficulty of the task is increased.

Animals

Unilateral and bilateral cortical spreading depression interferes with radial maze performance in rats.

Seven rats with implanted cortical electrodes were trained in a 12-arm radial maze to asymptomatic performance (1.38 errors per trial). Single waves of cortical spreading depression (CSD) were elicited by application of cathodal current to the parieto-occipital cortex and monitored by suppression of callosal responses in the frontal cortex. Bilateral CSD elicited before the trial caused a small increase of error incidence in choices 1-6 but did not affect accuracy of choices 7-12. Bilateral CSD between choices 6 and 7 increased error incidence in the second half of the trial from 1.33 to 2.84, i.e. almost to the chance level of 3.0. Unilateral CSDs elicited before the first half of the trial in one hemisphere and in the same or in the contralateral hemisphere before the second half of the trial caused similar deterioration of performance in choices 7-12 (2.4 and 2.1 errors, respectively). It is concluded that the CSD effects have both proactive and retroactive components and that the working memory record is not lateralized at the cortical level.

Animals

Post-trial flicker stimulation interferes with spatial memory in the Morris water maze.

Rats (n = 20) trained under monocular viewing conditions in the working memory version of Morris water maze task received daily a single acquisition trial with a new location of the invisible escape platform followed after 15 min by a single retrieval trial. Escape latency decreased by 50% during retrieval. Flash stimulation (20 Hz, 0.6 J) during the entire 15-min delay disrupted retention, but this effect was not observed when the flashes started 3 or 5 min after acquisition. It is concluded that successful place learning requires a brief interference-free post-acquisition interval.

Animals

Radial maze in the water tank: an aversively motivated spatial working memory task.

An 8-arm radial maze with 40 X 40 X 12 cm channels was inserted into a circular tank (120 cm in diameter, 60 cm high) filled 30 cm deep with 25 degrees C opaque water. Rats (n = 13) had to escape from the central area of the maze (30 cm in diameter) onto an invisible bench (1 cm below water surface) at the far end of each channel. Twenty sec after each choice the bench was collapsed and the animal was forced to choose again until all 8 channels had been visited. From the very beginning rats performed better than chance. The acquisition and performance of this aversively motivated radial maze test is similar as in conventional elevated 8-arm radial mazes.

Animals

On-demand platform improves accuracy of the Morris water maze procedure.

In order to prevent chance finding of the hidden target in the Morris water tank task, the rigid underwater platform is replaced with a collapsible platform, resting at the bottom of the pool. A computerized videosystem tracks the rat's movement across the pool and raises the platform when the animal has stayed in the target area for a predetermined time. Acquisition of the task with the collapsible platform proceeds at a similar rate as with the rigid platform when the criterion conditions are easy (target distance 15 cm, target time 2.5 s), but gradually deteriorates when the target time increases to 10.0 s. Successful solution of the modified task requires accurate localization of the target under open loop conditions and is thus well suited for investigation of the fine structure of the cognitive maps and of their changes induced by lesions or drugs.

Animals

Persistence of working memory of rats in an aversively motivated radial maze task.

The effects of various within-trial delays on the performance of rats in an 8-arm radial water maze (RWM) were investigated. Rats (n = 13) were trained to escape from 25 degrees C opaque water onto a submerged bench situated at the far end of each channel of the maze. After 20 s the chosen bench was collapsed and the rat had to return to a central platform, 1 cm above water level. After 15 s the platform was lowered and the animal was forced to choose again. This was repeated until all 8 channels had been visited. After 30 daily trials the mean number of correct choices per trial (first 8 choices) was 7.8. In Experiment 1, delays from 40 min up to 21 h were inserted between choices 4 and 5. The number of revisited channels (errors) in the second half of a trial increased rapidly with the duration of the delay, and was not significantly different from chance at 640 min. In Experiment 2, delays of 2.5, 5, 10 or 20 min were inserted between individual choices. Again, performance deteriorated with the duration of the delay. When the incidence of errorless trials was analyzed, performance was not significantly different from random at 5 min inter-choice delays. Comparison with conventional radial maze studies indicates that spatial working memory in the RWM has a slower, but also exponential decay.

Animals

Substitution of natural conditioned and unconditioned stimuli by artificial stimuli does not prevent acquisition of conditioned taste aversion in rats.

Attempts to replace a natural conditioned stimulus (taste) by electrical stimulation and a natural unconditioned stimulus (gastrointestinal disorder) by intracranial application of harmaline in the conditioned taste aversion (CTA) paradigm are described. The taste is replaced either by electrical stimulation of taste receptors of the tongue or by intracranial self-stimulation of the lateral hypothalamus, both triggered by licking. Both stimuli lose their rewarding properties when paired with gastrointestinal distress whereas self-stimulation triggered by nose poking is not affected by the same procedure. The unconditioned stimulus was replaced successfully by intracerebral injection of harmaline hydrochloride. The effect of the injection of 3-6 micrograms harmaline into the region of the inferior olive is comparable to that of systemic injection of 10 mg/kg harmaline. Electrophysiological analysis of the effect of locally and systemically applied harmaline indicates that the drug probably elicits CTA by activation of bulbar structures including the lateral reticular nucleus and lateral vestibular nucleus.

Animals

Central mediation of the conditioned taste aversion induced in rats by harmaline.

The assumption that drugs used as unconditioned stimuli in conditioned taste aversion (CTA) studies act centrally was tested by comparing the effects of systemic and intracerebral injections of harmaline hydrochloride (H) in 340 rats. Intraperitoneal injection of 5-20 mg/kg but not of 2.5 mg/kg H administered 5 min after 15-min saccharin (0.1%) drinking decreased saccharin-water preference in a two-choice retention test, performed 48 h later, from 55% to 20%. Since CTA was not diminished when H (10 mg/kg) was injected into rats anesthetised immediately after saccharin drinking by pentobarbital (40 mg/kg), H (1.7-50 micrograms) was administered intracerebrally to anesthetised rats fixed in the stereotaxic apparatus. Injection of 3-6 micrograms H into the inferior olive elicited CTA comparable to that of systemic injection of 10 mg/kg H. Injections of 6 and 50 micrograms H into cerebellum and bulbar reticular formation elicited weaker CTA while neocortical, hypothalamic and mesencephalic applications were ineffective. CTA could also be elicited when 50 micrograms but not 6 micrograms H was injected into the inferior olive 1 or 2 h after saccharin drinking. This delay-dependent effect and failure of non-contingent H administration to change saccharin preference indicates that the H-induced CTA is not contaminated by a non-specific increase in neophobia. It is concluded that H probably elicits CTA by activation of caudal bulbar structures, including the nucleus of the solitary tract, area postrema and lateral reticular formation.

Alkaloids

Persistence of spatial memory in the Morris water tank task.

Persistence of the spatial memory record was examined in 30 rats overtrained in the working memory version of the Morris water tank task. In Experiment 1, the animal had to find during the acquisition trial an invisible underwater platform randomly located at one of 4 possible sites in the pool. Retention test was performed 1 min, 60 min, 4 h or 24 h later with the same position of the platform and same or changed position of the start. Whereas in the acquisition trials the rats reached the goal after 12 s on average, the latency in the retrieval trials increased with the acquisition-retrieval interval. It was 5 s with the 1-min delay and exponentially approached, but did not quite reach the acquisition trial latency with the 24-h delay. In Experiment 2 the rats were started from the same position of the tank to goal positions changing from trial to trial in a prearranged sequence. There were either 1-h or alternating 1-min and 2-h intervals between the 6 daily trials. The latencies were long during the first trial and whenever the goal changed and short when the goal remained the same as on the previous trial. The latencies were not significantly influenced by intertrial interval in the 1 min to 2 h range. It is concluded that the decay of spatial memory in the water tank task is slow and is little affected by proactive interference.

Animals

The effect of hypothermia on the rat's spatial memory in the water tank task.

The effect of hypothermia on the retention of the water tank navigation task has been examined in 21 male hooded rats. After a 3-min swimming test on Day 1 the animals were trained on Days 2 and 3 (2 X 12 trials) to find a small submerged platform 1 cm below the surface of a large pool (120 cm in diameter) of opaque water. On Day 4, the rats were divided into three groups (n = 7) which were cooled to colonic temperatures of 22-24 degrees C (H1), 25-27 degrees C (H2), and 28-31 degrees C (H3), respectively, and given 12 retrieval trials in the water tank. Average escape latencies increased from 6 s in normothermic rats on Day 3 to 33, 19, and 12 s on Day 4 in the H1, H2, and H3 groups, respectively. Under the same testing conditions the performance of groups H1, H2, and H3 improved on Day 5 to 20, 8 and 6 s, respectively. It is concluded that spatial memory retrieval is resistant to mild hypothermia (30 degrees C), but that it is severely impaired at body temperatures below 25 degrees C. Reacquisition of the task is slowed down but not fully prevented in deep hypothermia.

Animals