The positive allosteric modulator of α7 nicotinic acetylcholine receptors, 3-furan-2-yl-N-p-tolyl-acrylamide, enhances memory processes and stimulates ERK1/2 phosphorylation in mice

Behav Brain Res. 2016 Apr 1;302:142-51. doi: 10.1016/j.bbr.2016.01.002. Epub 2016 Jan 8.

Abstract

To determine whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a positive allosteric modulator of α7 nicotinic acetylcholine receptors (nAChRs), improves memory processes, passive avoidance tests were conducted in male mice after acute and chronic treatments. To determine the neuronal mechanisms underlying the promnesic activity elicited by PAM-2, the effect of this ligand on α7 nAChR up-regulation and ERK1/2 phosphorylation was assessed in the hippocampus and prefrontal cortex. The results indicate that: (1) PAM-2 improves memory acquisition/consolidation after acute treatment (Day 2) and memory consolidation after chronic treatment (Day 22). Although no effect was observed on α7 nAChR up-regulation, the chronic, but not acute, PAM-2 treatment increases ERK1/2 kinase phosphorylation, (2) the promnesic activity of PAM-2 was inhibited by methyllycaconitine, a selective α7-antagonist, confirming the role of α7 nAChRs, (3) a synergistic (acute) effect was observed between inactive doses of PAM-2 (0.1 mg/kg) and DMXBA (0.3 mg/kg), a selective α7-agonist, and (4) PAM-2 reversed the memory impairment elicited by scopolamine, a muscarinic antagonist. The results demonstrate that PAM-2 presents promnesic activity mediated by α7 nAChRs, and is able to trigger ERK1/2 phosphorylation only after chronic treatment.

Keywords: DMXBA; ERK1/2 phosphorylation; Memory; Nicotine; Positive allosteric modulator; passive avoidance; α7 Nicotinic acetylcholine receptor; α7 Up-regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / pharmacology*
  • Allosteric Regulation / drug effects
  • Analysis of Variance
  • Animals
  • Dose-Response Relationship, Drug
  • Furans / pharmacology*
  • Locomotion / drug effects
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Memory / drug effects*
  • Mice
  • Muscarinic Antagonists / pharmacology
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology*
  • Phosphorylation / drug effects
  • Psychomotor Performance / drug effects
  • Scopolamine / pharmacology
  • Time Factors
  • alpha7 Nicotinic Acetylcholine Receptor / metabolism*

Substances

  • 3-furan-2-yl-N-p-tolylacrylamide
  • Acrylamides
  • Furans
  • Muscarinic Antagonists
  • Nicotinic Agonists
  • alpha7 Nicotinic Acetylcholine Receptor
  • Nicotine
  • Scopolamine