Cholinergic gating of hippocampal auditory evoked potentials in freely moving rats

Eur Neuropsychopharmacol. 2013 Aug;23(8):988-97. doi: 10.1016/j.euroneuro.2012.08.014. Epub 2012 Sep 10.

Abstract

As perturbations in auditory filtering appear to be a candidate trait marker of schizophrenia, there has been considerable interest in the development of translational rat models to elucidate the underlying neural and neurochemical mechanisms involved in sensory gating. This is the first study to investigate the effects of the non-selective muscarinic antagonist scopolamine, the muscarinic M1 antagonist biperiden and the cholinesterase inhibitor donepezil (also in combination with scopolamine and biperiden) on auditory evoked potentials (AEPs) and sensory gating. In the saline condition, only the N50 peak displayed sensory gating. Scopolamine and biperiden both disrupted sensory gating by increasing N50 amplitude for the S2 click. Donepezil was able to fully reverse the effects of biperiden on N50 sensory gating, but had residual effects when combined with scopolamine; i.e., it enhanced sensory gating by increasing N50 amplitude of the S1 stimulus. Donepezil by itself improved sensory gating by enhancing N50 amplitude of S1, and reducing N50 amplitude of the S2 click. In conclusion, due to its relatively more selective effects biperiden is to be preferred over scopolamine as a means for pharmacologically inducing cholinergic impairments in auditory processing in healthy rats. Changes in auditory processing and sensory gating induced by cholinergic drugs may serve as a translational model for aging instead of schizophrenia.

Keywords: Amp; Animal model; Auditory evoked potential; Biperiden; Donepezil; Lat; Muscarinic; SG; Scopolamine; Stim; Stimulus; Treat; Treatment; amplitude; decreased; increased; latency; n.s.; not significant; sensory gating; ↑; ↓.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / metabolism
  • Animals
  • Behavior, Animal / drug effects
  • Biperiden / analogs & derivatives
  • Biperiden / pharmacology
  • Cholinergic Neurons / drug effects
  • Cholinergic Neurons / metabolism*
  • Cholinesterase Inhibitors / pharmacology
  • Disease Models, Animal
  • Donepezil
  • Electroencephalography / drug effects
  • Evoked Potentials, Auditory* / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Indans / pharmacology
  • Male
  • Muscarinic Antagonists / pharmacology
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Piperidines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Muscarinic M1 / antagonists & inhibitors
  • Receptor, Muscarinic M1 / metabolism
  • Schizophrenia / chemically induced
  • Schizophrenia / metabolism
  • Scopolamine / pharmacology
  • Sensory Gating* / drug effects

Substances

  • Cholinesterase Inhibitors
  • Indans
  • Muscarinic Antagonists
  • Nerve Tissue Proteins
  • Piperidines
  • Receptor, Muscarinic M1
  • biperiden lactate
  • Biperiden
  • Donepezil
  • Scopolamine