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Male Wistar rats were given a bilateral or a unilateral transection of the fimbria-fornix; subsequently they were kept in standard laboratory housing conditions or in enriched environments for 6 weeks, after which they were tested in the Morris maze. In the acquisition phase of the experiment rats with a bilateral lesion of the fimbria-fornix were markedly impaired in their ability to locate the hidden platform, while rats with unilateral lesions displayed no such impairment. However, rats with a bilateral lesion displayed a less severe deficit when they had been housed postoperatively in the enriched environment. In the retention phase of the experiment rats with a bilateral lesion swam markedly less time in the platform zone only when they had been housed in standard conditions. They also spent more time in the edge zone than the oth...
Male Wistar rats received bilateral Fimbria lesions and were postoperatively housed in either standard social conditions or in impoverished conditions (one rat per cage) for 2 weeks in experiment I, and for 7 months in experiment II. The effects of lesion and housing conditions were investigated in the Morris maze spatial orientation task. Fimbria lesions increased the latency to reach the platform during acquisition in both experiments, which indicates that functional recovery of the Morris maze impairment does not occur in 7 months time. Post-operative impoverishment for 2 weeks or for 7 months reduced the lesion induced deficit in Morris maze acquisition, while it had a more general effect in the trial without platform. Interestingly, the impoverishment effects were not more severe after 7 months, but even less easily detected. Thes...
Microinjection of N-methyl--aspartic acid (NMDA, 300 ng/3 l) into the left lateral ventricle causes a substantial increase in locomotor activity which can be significantly reduced by a chronic pretreatment with the ACTH(4–9) analogue ORG 2766 (1 g/0.5 ml saline, subcutaneous (s.c.) every day for 7 days, last injection 24 h before the NMDA-injection). A single dose of ORG 2766 (1 ng/1 l) injected into the left central amygdaloid nucleus 30 min before the NMDA-injection was equally effective in reducing the increase in locomotion. Furthermore it counteracted the predominance of contralateral turning induced by the NMDA-injection. The data give support for the idea that ORG 2766 excerts its effects on behavior and neural recovery by modulating NMDA receptor activity in the brain.
The ACTH(4–9) analog ORG2766 has been known to affect recovery of damaged functions resulting from injury to neural tissue. The peptides efficacy has often been ascribed to a facilitation of existing recovery, and immediate treatment seemed a prerequisite for efficacy. However, various results in other recovery paradigms do not refer to the neurotrophic properties of the peptide, but rather ascribe the effectiveness of ORG2766 to a general change in attention that indirectly affects functional recovery. Such a change in state is theoretically independent of the occurrence of spontaneous recovery, and, thus, treatment would not be required to coincide with recovery immediately after the damage. To see if ORG2766 can influence the recovery of function without the simultaneous occurrence of spontaneous recovery, this study employed a dela...
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