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 neurokin in substance P (SP) can enhance adaptive graft effects on learning and memory functions in animals with lesions of the hippocampus. Adult ma le Wistar rats received a bilateral kainic acid (KA) lesion of the dor sal hippocampus. One week postlesion, bilateral grafts of fetal hippoc ampal tissue suspension were applied into the damaged region in half o f the animals, whereas the other half received sham transplants (physi ological saline). Animals of the control group received a bilateral sh am lesion of the hippocampus and sham transplants. One week after tran splantation 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 inhibito ry avoidance task. All animals received LP injections of either SP (5 or 50 mu g/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 th e water maze and avoidance task, application of the substances was per formed 5 h after testing. For the conditioned place preference test, t he conditioning trials were performed immediately after drug administr ation; the test trials were given 24 h later. Chronic administration o f 50 mu g/kg SP, but not 5 mu g/ kg SP, was found to improve water maz e performance in lesioned animals with and without grafts. Unexpectedl y, the lesion group with the graft without additional SP treatment was not superior to the lesion group devoid of the graft in this task. Th e rats without lesions of the hippocampus still showed a conditioned p lace preference to 50 mu g/kg SP after 9 weeks of repeated SP applicat ions. In the inhibitory avoidance task, the grafts facilitated retenti on performance independent of whether SP treatment was given. The morp hological analysis of the transplants revealed higher graft volumes an d a higher diameter of large pyramidal neurons (>10 mu m) in rats chro nically treated with 50 mu g/kg SP.