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

Neuropharmacology. 2006 Mar;50(4):412-20. doi: 10.1016/j.neuropharm.2005.10.002. Epub 2005 Nov 18.

Abstract

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.

MeSH terms

  • Animals
  • Anxiety
  • HeLa Cells
  • Humans
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Memory Disorders / chemically induced*
  • Memory Disorders / prevention & control*
  • Motor Activity / drug effects
  • Nootropic Agents / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Recognition, Psychology / drug effects
  • Scopolamine / pharmacology*
  • Tryptamines / pharmacology*
  • Tryptamines / physiology*

Substances

  • 5-methoxy-2-phenyl-N,N-dimethyltryptamine
  • Nootropic Agents
  • Receptors, Serotonin
  • Tryptamines
  • serotonin 6 receptor
  • tryptamine
  • Scopolamine