Effects of BIM-22015, an analog of ACTH4-10, on functional recovery after frontal cortex injury.
Male rats, 90-100 days old, with frontal cortex lesions were given either subcutaneous sterile water (SW) as a vehicle control or 1, 10, or 100 micrograms of BIM-22015 every other day for 20 days. Brain-injured subjects tested in the Morris water maze with either 10 micrograms BIM-22015 or SW took significantly more trials than sham-operated rats to locate a submerged platform eight consecutive times within 60 s. The animals given 1 or 100 micrograms BIM-22015 took significantly fewer trials to reach criterion than brain-injured animals in the other drug treatment groups. On a percentage of savings, measured 8 days after reaching criterion, the brain-injured subjects given 1, 10, or 100 micrograms BIM-22015 did not differ from sham-operated rats. In contrast, the brain-injured animals given SW took longer to find the submerged platform than they did during the initial training. To assess long-term effects of the ACTH analog treatment, rats were trained on a delayed spatial alternation task 30 days after receiving the last injection. On this task, brain-injured rats treated with the 10-micrograms dose performed significantly better than those given sterile water. Acetylcholinesterase (AChE)-labeled neurons counted in the nucleus basalis magnocellularis indicated that rats with frontal cortex damage given the 10-micrograms treatment did not differ from the sham controls and had significantly more AChE-positive neurons than injured counterparts treated with SW or 100 micrograms.
Attella
M J
MJ
Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545.
Hoffman
S W
SW
Pilotte
M P
MP
Stein
D G
DG
D000110:Acetylcholinesterase / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001931:Brain Mapping; D002799:Cholinergic Fibers / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D004924:Escape Reaction / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000293:injuries*; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D009949:Orientation / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D012153:Retention, Psychology / Q000187:drug effects; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D000324:Adrenocorticotropic Hormone; D000110:Acetylcholinesterase; C011394:ACTH (4-10)