Acute ampakine treatment ameliorates age-related deficits in long-term potentiation

Biomed Pharmacother. 2016 Dec:84:806-809. doi: 10.1016/j.biopha.2016.10.016. Epub 2016 Oct 7.

Abstract

Memory loss observed as a consequence of aging is paralleled by a down-regulation of AMPA-type glutamate receptors (AMPARs) that mediate fast excitatory synaptic transmission. Activation of these receptors enhances long-term potentiation (LTP), a neuronal process demonstrated to be crucial for memory storage and thought to be a cellular substrate of learning and memory. In the present studies, we determined that LTP was reduced in aged rats when compared to young rats and that acute treatment with CX1846, a novel AMPAR positive allosteric modulator, fifteen minutes prior to tetanic stimulation completely reversed the significant deficit in LTP observed in aged rats. These results suggest that CX1846 might be useful for the treatment of age-related memory impairments.

Keywords: AMPA receptor; Ampakine; BDNF; Cognitive deficit; LTP; Memory formation.

MeSH terms

  • Aging / drug effects*
  • Aging / physiology
  • Allosteric Regulation / drug effects
  • Allosteric Regulation / physiology
  • Animals
  • Excitatory Amino Acid Agonists / chemistry
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Agonists / therapeutic use
  • Long-Term Potentiation / drug effects*
  • Long-Term Potentiation / physiology
  • Memory Disorders* / drug therapy
  • Rats
  • Rats, Inbred F344
  • Receptors, AMPA / agonists*
  • Receptors, AMPA / physiology
  • Treatment Outcome

Substances

  • Excitatory Amino Acid Agonists
  • Receptors, AMPA