Dual effects of bryostatin-1 on spatial memory and depression.
Dementia and depression are clinical symptoms commonly associated in patients. Emerging evidence suggests that the two diseases share many profiles in their development and underlying neural/molecular mechanisms. Thus, interest is raised in developing new classes of antidepressant agents with activity of cognitive enhancement. Here, we show that bryostatin-1, a protein kinase C substrate activator, at bilateral intracerebroventricular doses of 0.64 or 2 pmol/site, significantly enhanced learning and memory of rats in a spatial water maze task. When applied at the doses at which it exhibits memory-enhancing activity, bryostatin-1 showed a significant antidepressant activity, as determined in an open space swim test. Both effects were not observed when a smaller dose was administered and were largely eliminated by co-administration of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), a protein kinase C inhibitor. These results support the hypothesis that memory processing and mood regulation share common neural mechanisms. Restoring impaired mood regulation with antidepressant agents that also exhibit memory-enhancing activity may represent one of the new strategies in the fight against depression associated with memory impairments.
Sun
Miao-Kun
MK
Blânchette Rockefeller Neurosciences Institute, 9601 Medical Center Drive, Johns Hopkins Academic and Research Building, Room 319, Rockville, MD 20850, USA. mksun@brni-jhu.org
Alkon
Daniel L
DL
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D054713:Bryostatins; D003863:Depression / Q000188:drug therapy; D007276:Injections, Intraventricular; D018942:Macrolides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000928:Antidepressive Agents; D054713:Bryostatins; D018942:Macrolides; C046785:bryostatin 1; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C