Subchronic use of rivastigmine increases procognitive flexibility across multimodal behavioral tasks in healthy male rats

Behav Brain Res. 2019 Dec 30:376:112077. doi: 10.1016/j.bbr.2019.112077. Epub 2019 Sep 6.

Abstract

Rivastigmine (RVT) is a reversible inhibitor of cholinesterase approved worldwide for the treatment of cognitive dysfunctions, especially in Alzheimer's disease. Most previous pre-clinical studies have examined the effects of RVT treatment in a wide variety of pathological research models. Nonetheless, the effects of this drug on sensorimotor gating, memory, and learning tasks in healthy subjects remains unclear. In this study, we investigate the procognitive effects of RVT treatment in healthy rats through sensorimotor gating evaluations (measured as prepulse inhibition of the acoustic startle reflex), active avoidance learning, and spatial memory learning in a radial maze. There is an increase in the amplitude of the startle reflex in RVT-treated rats compared to the control groups, whereas the latency remained constant. Sensorimotor gating values were also incremented compared to those values from controls. In active avoidance, rats treated with RVT learned faster to successfully perform the task compared to controls, but afterwards all groups exhibited virtually identical results. During the sessions in the radial maze, RVT-treated rats committed fewer errors in both the working and reference memory compared to controls. All in all, our results support the hypothesis that RVT treatment may entail procognitive effects in healthy subjects.

Keywords: Acetylcholinesterase; Active avoidance; Prepulse inhibition; Radial maze; Sensorimotor gating; Startle reflex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Avoidance Learning / physiology
  • Brain / physiology
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterases / metabolism
  • Cognition / physiology
  • Male
  • Maze Learning / physiology
  • Prepulse Inhibition / drug effects
  • Rats
  • Rats, Wistar
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology*
  • Rivastigmine / metabolism
  • Rivastigmine / pharmacology*
  • Sensorimotor Cortex / drug effects*
  • Sensory Gating / physiology
  • Spatial Learning / physiology
  • Spatial Memory / physiology

Substances

  • Cholinesterase Inhibitors
  • Cholinesterases
  • Rivastigmine