BGC20-761, a novel tryptamine analog, enhances memory consolidation and reverses scopolamine-induced memory deficit in social and visuospatial memory tasks through a 5-HT6 receptor-mediated mechanism.
Inhibition of 5-HT(6) receptors has been shown to improve memory consolidation, thus we tested whether a novel tryptamine analog with high affinity for 5-HT(6) receptors, BGC20-761 (5-methoxy-2-phenyl-N,N-dimethyltryptamine, PMDT), can enhance long-term memory. BGC20-761 (10 mg/kg i.p.) alone had no effect on social recognition in young rats, however, at doses of 5 mg/kg and 10 mg/kg i.p, BGC20-761 dose-dependently reversed a deficit of social recognition induced by scopolamine (0.4 mg/kg i.p.), an anticholinergic drug that impairs memory. BGC20-761 (10 mg/kg i.p.), scopolamine (0.2 mg/kg i.p.) or BGC20-761 + scopolamine had no effects on novel object discrimination in young rats (2 months). In mature rats (6 months), recognition of the novel object was improved following administration of BGC20-761. Scopolamine had no effect in object recognition. However, the addition of scopolamine disrupted the memory-enhancing effect of BGC20-761. Based on the high affinity of BGC20-761 for 5-HT(6) receptors, these cognitive enhancing effects are most likely mediated by 5-HT(6) receptor inhibition. The difference in effects of BGC20-761 in young vs. mature rats may reflect the status of memory consolidation in these different age ranges.
Mitchell
Ellen S
ES
1-University of Washington, Harborview Medical Center, Seattle, 98104, USA.
Hoplight
Blair J
BJ
Lear
Sean P
SP
Neumaier
John F
JF
D000818:Animals; D001007:Anxiety; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D021641:Recognition, Psychology / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology* / Q000502:physiology*
C511537:5-methoxy-2-phenyl-N,N-dimethyltryptamine; D018697:Nootropic Agents; D011985:Receptors, Serotonin; D014363:Tryptamines; C097216:serotonin 6 receptor; C030820:tryptamine; D012601:Scopolamine