Vigilance‐Controlled Quantified EEG in Safety Pharmacology

N. Dürmüller1, R.D. Porsolt1, R. Scherschlicht2

1 Porsolt and Partners Pharmacology, Boulogne Billancourt, France, 2 Science Writing, Inzlingen, Germany
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 10.6
DOI:  10.1002/0471141755.ph1006s11
Online Posting Date:  May, 2001
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Abstract

The vigilance‐controlled quantified EEG can be used either as a safety, or as a discovery pharmacology procedure. Put strategically into the preclinical development process of a drug, it can be useful for making the decision about the future research direction to be taken. The experimental approach described in this unit is based on the rat EEG. Even though there are considerable differences in function and structure between human and rat brain, the EEG response to psychoactive drugs and convulsants is similar in the two species. Thus, the rat EEG is generally a reliable predictor for human CNS drug effects.

     
 
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Table of Contents

  • Strategic Planning
  • Basic Protocol 1: Electrode Implantation
  • Basic Protocol 2: Vigilance‐Controlled Quantified EEG in Implanted Rats
  • Support Protocol 1: Cable Construction
  • Commentary
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Electrode Implantation

  Materials
  • 320 to 350‐g male Wistar rats
  • 37% (v/v) formaldehyde
  • Injectable anesthetic (sodium pentobarbital recommended)
  • Disinfectant solution (e.g., Mercryl)
  • 3% (v/v) H 2O 2 solution
  • Physiological saline (0.15 M NaCl), sterile
  • Dentalon Plus dental acrylate (Heraeus Kulzer)
  • ∼0.5 mm thick, bare copper wire and 2 × 4.4‐mm titanium screws (Straumann; surface‐electrodes; see Internet Resources)
  • Flat and cutting pliers (surface electrodes)
  • Solder and soldering iron (surface electrodes)
  • 130‐µm diameter twisted Teflon‐coated platinum/iridium wires (A‐M Systems; depth‐electrodes; see Internet Resources) fitted with type 220‐S02 Amphenol contacts (WirePro)
  • ∼5 cm flexible plastic tubing (inner diameter 0.8‐mm, outer diameter 1.2‐mm)
  • 18‐G × 1½‐in. hypodermic needle, blunt
  • 2.5‐ml disposable syringe
  • Electric clippers
  • SAS‐4100 stereotaxic frame with holder and ear‐plug adapters for chronically implanted animals (ASI Instruments)
  • Lamp, adjustable in position and light intensity (e.g., illuminator equipped with a tungsten/argon max. 600 ftc reflector bulb; Harvard Apparatus)
  • Fine surgical equipment: scalpel, retractor, bone scraper, scissors, forceps, needle holder, needles, sutures
  • Cotton swabs, buds (e.g., Q‐tips), and absorbent tissue tips (triangular: base ∼5 to 10 mm, height ∼20 mm)
  • Dental drill (e.g., motor: model 831, KaVo EWL; handpiece: model 434, W & H Dentalwerk; see Internet Resources)
  • Fine screwdriver
  • Small plastic dishes (diameter 3 to 4 cm) and fine spatula
  • 9 Mcintyre STC‐89P1‐220 miniature connectors (height 12‐mm, shaft diameter 8.8‐mm; Ginder Scientific)
  • Curved artery forceps
  • Cage with flat top cover

Basic Protocol 2: Vigilance‐Controlled Quantified EEG in Implanted Rats

  Materials
  • Rats implanted with cortical and hippocampal electrodes (see protocol 1)
  • Antistatic spray (e.g., Pliz, Johnson wax)
  • Forms for hardware setting documentation
  • Treadmills with 30 × 10 × 25‐cm Plexiglas recording cubicles (Hoffmann‐La Roche)
  • Absorbent paper
  • Recording cables (see protocol 3 and Fig. )
  • Turning commutators (Hoffmann‐La Roche)
  • Lablinc V, model V75‐01 signal conditioning system (Coulbourn)
  • Notch filter
  • Data acquisition system (DAS802 boards, Keithley; ASYST‐written data acquisition program for Fast Fourier Transform, NumerikLab)
  • Personal computers: one for each recording station and an additional processor with CD writer
  • Data analysis system:
  •  ASYST‐written analysis program: for Fast Fourier Transform, outlier correction, and averaging (NumerikLab)
  •  Microsoft Excel: for statistical analysis and data presentation
  • Data transfer system: Hub Model DE 809TC (D‐Link); EtherlinkIII and Fast Etherlink XL cards (3Com)
  • Data archiving system: CD writer Plus 7200e (Hewlett‐Packard) and DirectCD software (Adaptec)

Support Protocol 1: Cable Construction

  • 7 0.1‐mm diameter wires of different colors (PVC isolated multicore)
  • 3‐mm diameter tubular braided tin plated copper wire
  • 0.075 × 12–mm Teflon tape
  • 2 connectors (animal side and commutator side)
  • Silicon rubber
  • ∼4 × 2 × 1‐cm foam pad
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Figures

Videos

Literature Cited

Literature Cited
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Internet Resources
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