SEROTONERGIC FIBERS DEGENERATING IN THE AGING RAT-BRAIN OR SPROUTING FROM GRAFTED FETAL NEURONS ARE NOT AFFECTED BY THE NEUROTROPHIC ACTH ANALOG ORG-2766

The effects of chronic treatment with the purported neurotrophic factor ACTH(4-9) analogue Org 2766 were studied on age-related degeneration of serotonergic fibres and on gliosis in the rat hippocampus and caudate putamen complex. In addition, the potential growth-promoting effects of Org 2766 were investigated on fetal serotonergic cells implanted in a previously denervated hippocampus of young adult rats. Chronic treatment of rats from the age of 11 months to 17-18 months did not affect the incidence of aberrant serotonergic fibres in the caudate-putamen complex or the fibres densities in the hippocampus or the caudate-putamen complex. Gliosis was unaffected by Org 2766 treatment as indicated by increased number and staining intensity of glial fibrillary acidic protein-immunoreactive cell bodies in both brain areas. Grafting of fetal raphe cells in young adult rats caused a time-dependent reinnervation of the previously denervated hippocampus. The reinnervation was not affected by treatment of the rats with Org 2766 for 4 weeks following implantation.