ACTH(4-9) analog ORG2766 treatment 7 months delayed still improves morris maze performance of fimbria-lesioned rats.
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 delay of 7 months after the occurrence of a fimbria lesion before ORG2766 was administered. The selective fimbria lesion produced an impairment in Morris maze performance, which could be attenuated by chronic treatment with ORG2766 immediately after the lesion as well as after 7 months. With respect to spatial orientation, no improvement is assessed in untreated lesioned rats, as the impairment of Morris maze performance in untreated fimbria-lesioned rats is as severe as right after the lesion. The data indicates that efficacy of the ACTH(4-9) analog does not rely on the acceleration of spontaneous recovery processes in this paradigm. The behavioral effects of ORG2766 are discussed in the context of a peptide-induced state of enhanced attention.
Van Rijzingen
I M
IM
Rudolf Magnus Institute for Neurosciences, Utrecht, Netherlands.
Van Doremalen
E
E
Josephy
M
M
Gispen
W H
WH
Spruijt
B M
BM
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D006624:Hippocampus / Q000033:anatomy & histology / Q000293:injuries* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects / Q000502:physiology
D010446:Peptide Fragments; C028024:ACTH (4-9); D000324:Adrenocorticotropic Hormone