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Eur J Pharmacol. 2005 Apr 4;512(1):43-51.

Dual effects of bryostatin-1 on spatial memory and depression.

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Blânchette Rockefeller Neurosciences Institute, 9601 Medical Center Drive, Johns Hopkins Academic and Research Building, Room 319, Rockville, MD 20850, USA.

Erratum in

  • Eur J Pharmacol. 2005 Nov 21;525(1-3):171.


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.

[Indexed for MEDLINE]

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