The NK3 receptor agonist senktide ameliorates scopolamine-induced deficits in memory for object, place and temporal order

Neurobiol Learn Mem. 2012 Feb;97(2):235-40. doi: 10.1016/j.nlm.2011.12.007. Epub 2011 Dec 22.

Abstract

Senktide, a potent neurokinin-3 receptor (NK3-R) agonist, increases acetylcholine (ACh) release in the striatum, the prefrontal cortex (Schäble et al., 2011), the amygdala and hippocampus, presumably via postsynaptic mechanisms. A promnestic action of NK3-R agonists has been described in a variety of learning/memory tasks. The memory-enhancing effects of NK3-R agonists and their activating influence on ACh suggest a possible role of the NK3-R in learning and memory via cholinergic modulation. Deterioration of the cholinergic system in the basal forebrain has been associated with learning and memory deficits and cholinergic agents have promnestic effects in a variety of learning paradigms. The anticholinergic drug, scopolamine, a muscarinic ACh receptor antagonist, incurs deficits in a variety of learning tasks and provides a useful tool to investigate the role of the cholinergic systems in mechanisms underlying learning and memory. The aim of this study was to ascertain the effect of the NK3-R agonist, senktide, in the scopolamine-induced deficit model. We hypothesized that senktide treatment would attenuate scopolamine-induced (subcutaneous--s.c. 0.75 mg/kg) memory impairment in three novelty preference paradigms based on spontaneous object exploration: namely object recognition, object-place recognition and object recognition for temporal order. Administration of senktide reversed the scopolamine-induced memory deficits by re-establishing object recognition (s.c. 0.2 mg/kg), object-place recognition (0.2 and 0.4 mg/kg), as well as object recognition for temporal order (0.4 mg/kg) in adult Wistar rats. These results indicate memory enhancing effects of senktide in animals subjected to scopolamine-induced memory impairments and indicate that the promnestic action of NK3-R agonists is mediated by muscarinic cholinergic mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy*
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / therapeutic use
  • Rats
  • Rats, Wistar
  • Receptors, Neurokinin-3 / agonists*
  • Recognition, Psychology / drug effects
  • Scopolamine
  • Substance P / analogs & derivatives*
  • Substance P / pharmacology
  • Substance P / therapeutic use

Substances

  • Peptide Fragments
  • Receptors, Neurokinin-3
  • senktide
  • Substance P
  • Scopolamine