Attenuation of hippocampal kainic acid-induced seizures by substance P treatment.

Adult male Wistar rats (n = 21) received bilateral kainic acid lesions of their hippocampi. Over a period of 9 weeks the animals received daily IP injections of either 5 micrograms/kg or 50 micrograms/kg substance P (SP) or vehicle. Seizures provoked by the lesions were suppressed by the daily administration of the neuropeptide SP in a dose of 50 micrograms/kg for the whole period of observation. The neurokinin significantly (p < 0.01) reduced the number of seizures compared to the vehicle-treated animals.

Effects of chronic substance P treatment and intracranial fetal grafts on learning after hippocampal kainic acid lesions.

The purpose of this experiment was to investigate whether the neurokinin substance P (SP) can enhance adaptive graft effects on learning and memory functions in animals with lesions of the hippocampus. Adult male Wistar rats received a bilateral kainic acid (KA) lesion of the dorsal hippocampus. One week postlesion, bilateral grafts of fetal hippocampal tissue suspension were applied into the damaged region in half of the animals, whereas the other half received sham transplants (physiological saline). Animals of the control group received a bilateral sham lesion of the hippocampus and sham transplants. One week after transplantation surgery, the rats were tested in the place version of the Morris water maze over a period of 9 weeks. Then they were tested for SP-induced conditioned place preference and on a step-through inhibitory avoidance task. All animals received IP injections of either SP (5 or 50 micrograms/kg) or the SP vehicle (0.5 ml/kg). The treatment with SP or the vehicle was begun 1 week after transplantation and was performed 5 days a week over a period of 10 weeks. During behavioral tests in the water maze and avoidance task, application of the substances was performed 5 h after testing. For the conditioned place preference test, the conditioning trials were performed immediately after drug administration; the test trials were given 24 h later. Chronic administration of 50 micrograms/kg SP, but not 5 micrograms/ kg SP, was found to improve water maze performance in lesioned animals with and without grafts. Unexpectedly, the lesion group with the graft without additional SP treatment was not superior to the lesion group devoid of the graft in this task. The rats without lesions of the hippocampus still showed a conditioned place preference to 50 micrograms/kg SP after 9 weeks of repeated SP applications. In the inhibitory avoidance task, the grafts facilitated retention performance independent of whether SP treatment was given. The morphological analysis of the transplants revealed higher graft volumes and a higher diameter of large pyramidal neurons (> 10 microns) in rats chronically treated with 50 micrograms/kg SP.

A low-cost method to analyse footprint patterns.

Neurological dysfunction can be assessed by analysing footprint patterns and walking tracks. However, because such an analysis is very time consuming, we developed an MS-Windows program called FOOTPRINTS which facilitates the analysis of the commonly used measures and which is considerably quicker than manual scoring methods. The prints are scanned at a resolution of 75 dpi and stored as black and white bitmaps for further analysis. In order to validate the program, we analysed the footprint patterns of mice and rats, using both the program and the conventional manual scoring method. In the first study, the walking patterns of 3-, 14-, and 26-month-old Janvier Wistar rats were compared, and in the second the footprint patterns of C57BL mice were assessed. Comparison of the data obtained using the program and of the data obtained by manual scoring showed that the computer-based analysis gives reliable results. The program saves considerable time as the analysis took 1/8th of the time needed for manual evaluation.

Facilitation of learning in adult and aged rats following bilateral lesions of the tuberomammillary nucleus region.

In the present experiment, adult (3-month-old) and aged (31-month-old) rats received bilateral DC or sham-lesions in the region of the tuberomammillary (TM) nucleus before they were trained and tested on a one-trial step-through inhibitory avoidance task. Bilateral lesions of the TM nucleus led to significantly longer latencies in the step-through response during retention test in both adult and aged rats, indicative of superior learning of the task. Thus, lesions of the TM nucleus may have a facilitatory effect on learning and mnemonic functioning which is possibly related to a lesion-induced disinhibition or facilitation of reinforcement processes ("stamping-in") as revealed in previous studies.

The Morris water-escape task in mice: strain differences and effects of intra-maze contrast and brightness.

The Morris water-escape task is an extensively used experimental paradigm to assess the spatial discrimination performance and effects of brain lesions and drugs on this performance. In the first experiment, we compared the acquisition of this task by different strains (CFW1, BALB, NMRI, and C57BL) of mice and their performance in a probe trial. In a second experiment, C57BL mice were tested in Morris mazes where black and white tanks were combined with white or black platforms to investigate if and how the contrast between the tank and the platform affects the performance of the mice. In addition, four brightness conditions were compared to investigate whether or not the degree of brightness of the tank itself affects the learning performance. The results of these experiments indicated that 1. mice could readily learn the Morris task, 2. one of the contrast conditions affected the swimming speed, 3. the maze brightness per se did not affect water escape performance at all, and that 4. the swimming speed can strongly bias the outcome of Morris water-escape experiments in mice.

Repeated acquisition of a spatial navigation task in mice: effects of spacing of trials and of unilateral middle cerebral artery occlusion.

The working memory version of the Morris water escape task, the repeated acquisition task, consists of trial pairs in which an animal is started twice from the same start position. Animals have mastered this task when they need less time to find the platform in the second of the two trials. In this study, study, male C57BL mice were trained on this task with massed, spaced, or spaced delay trials in which there was a 90-min delay between the first and second trials of a pair. The mice trained with spaced trials learned the repeated acquisition task, whereas the mice trained with massed or spaced delay trials were not consistently able to do so. When the mice had reached a stable baseline performance, the middle cerebral artery (MCA) was occluded or the mice were sham-operated. Then, the effects of the MCA occlusion (MCA-O) on the performance in the repeated acquisition tasks were studied. MCA occlusion hardly affected the performance in this task, irrespective of the spacing condition of the trials, although surgery per se seemed to have a transient disruptive effect.