Chronic Intravenous Drug Self‐Administration in Rats and Mice

Morgane Thomsen1, S. Barak Caine2

1 University of Copenhagen, Copenhagen, 2 McLean Hospital‐Harvard Medical School, Belmont, Massachusetts
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.20
DOI:  10.1002/0471142301.ns0920s32
Online Posting Date:  August, 2005
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Abstract

Chronic intravenous drug self‐administration in rodents is a useful procedure for predicting the abuse liability of novel drugs in humans, for evaluating candidate treatments for drug abuse and dependence, and for studying the biological basis of addiction. This unit focuses on recent technical innovations for conducting long‐term studies of i.v. drug self‐administration behavior in healthy, freely moving rats and mice. Included are protocols for construction, implantation, and maintenance of chronic indwelling jugular catheters, commentary on critical parameters, a troubleshooting guide, and anticipated results.

Keywords: self‐administration; rat; mouse; cocaine; drug abuse; animal model

     
 
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Table of Contents

  • Strategic Planning
  • Basic Protocol 1: Construction of a Chronic Intravenous Catheter for Rats or MICE
  • Support Protocol 1: Construction of Self‐Administration Catheter Accessories
  • Basic Protocol 2: ID Chip Implantation
  • Basic Protocol 3: Self‐Administration Catheter Implantation in the Rat
  • Alternate Protocol 1: Catheter Implantation in the Mouse
  • Alternate Protocol 2: Implantation of a Second Self‐Administration Catheter
  • Support Protocol 2: Re‐Position Self‐Administration Catheter
  • Basic Protocol 4: Catheter Maintenance/Flushing
  • Basic Protocol 5: Ketamine/Midazolam Test of Self‐Administration Catheter Patency in Rats
  • Alternate Protocol 3: Ketamine/Midazolam Test of Self‐Administration Catheter Patency in Mice
  • Basic Protocol 6: Self‐Administration Training
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Construction of a Chronic Intravenous Catheter for Rats or MICE

  Materials
  • Medical‐grade silicone adhesive
  • Xylene solvent or a less toxic substitute (e.g., Hemo‐De, Fisher)
  • Silicone oil lubricant
  • Permanent non‐toxic fixative such as dental cement or resin (e.g., cranioplastic powder and liquid, Plastics One)
  • 1‐ml flushing syringe containing sterile water (see protocol 2)
  • Monofilament cloth‐nylon mesh (500‐µm, 12 × 24–in.; Small Parts)
  • Tubing:
    • For rats: medical‐grade silastic tubing, size 0.012‐in./0.31‐mm i.d. × 0.025‐in./0.64‐mm o.d. (Dow Corning)
    • For mice: medical‐grade silicone catheter tubing, 1.2 French, 0.007‐in./0.018‐mm i.d. × 0.16‐in./0.41‐mm o.d. × 25 feet (Access Technologies)
  • Scalpel
  • Needlenose pliers
  • Cannula guides with threaded plastic base: for rats: 22‐G, 5 mm; for mice: 26‐G, 5 mm (Plastics One)
  • Molds for making the catheter base (e.g., aluminum as shown in Fig. )

Support Protocol 1: Construction of Self‐Administration Catheter Accessories

  Materials
  • 22‐ and 26‐G needle with luer hub, 1/2‐in. (Small Parts)
  • Tygon tubing, 0.02‐in./0.51‐mm i.d. × 0.06‐in./1.52‐mm o.d.
  • 1‐ and 0.25‐ml syringes
  • Flexible plastic tubing, 0.010‐in./0.25‐mm i.d. × 0.030‐in./0.76‐mm o.d. (Tygon)
  • Nylon monofilament (e.g., 50‐lb capacity fishing line)
  • Protective covers: round standoff aluminum 6‐32 × 1/2–in., 0.25‐in. o.d. (Small Parts; requires special ordering)
  • 18‐G needle
  • Metal file

Basic Protocol 2: ID Chip Implantation

  Materials
  • Anesthesia: inhalant or injectable ( appendix 4B)
  • Rats or mice
  • 70% alcohol wipes
  • Hair clippers
  • Surgical scissors
  • Forceps
  • Hemostat with straight tip
  • Electronic ID chip for subcutaneous implantation (e.g., AVID Identification Systems)
  • Suture and needle holder or Castroviejo

Basic Protocol 3: Self‐Administration Catheter Implantation in the Rat

  Materials
  • Pre‐anesthetic, e.g., 5 mg/kg midazolam (Henry Schein veterinary supply), i.p. (1 ml/kg of a 5 mg/ml solution), optional
  • Antibiotic, e.g., 10 mg/kg amikacin‐C (Henry Schein veterinary supply), s.c. (1 ml/kg of a 10 mg/ml solution)
  • Two flushing syringes (see protocol 2): one containing sterile physiological saline and the other containing heparinized (30 USP U/ml) saline with antibiotic (e.g., cefazolin, 67 mg/ml or ticarcillin, 67 mg/ml)
  • Anesthesia, inhalant (e.g., halothane, isoflurane, or sevoflurane, mixed with oxygen), or injectable (e.g., Ketaset i.p., Fort Dodge Labs)
  • Rats
  • Eye ointment (lubricant)
  • Iodine prep pads
  • 70% ethanol
  • Saline containing antibiotic (e.g., gentamycin 8 mg/ml) for irrigation (to keep tissues from drying out during surgery)
  • Topical antibiotic (e.g., triple antibiotic ointment)
  • Postoperative analgesic, e.g., 5 mg/kg ketprofen, s.c. (1 ml/kg of a 5 mg/ml solution)
  • Rat food
  • Sterilized rat catheter (see protocol 1) and cap (see protocol 2)
  • Hair shaver
  • Scalpel blade (e.g., no. 15)
  • Large surgical scissors with blunt tips
  • Hemostat with curved tip
  • Two pairs of fine forceps with smooth curved tips—one slightly blunted and one sharp‐pointed (or both slightly blunted)
  • Smooth steel bar, ∼1‐mm thick and 5‐cm long, with blunt ends
  • Suture
  • Artery scissors (e.g., Bonn scissors)
  • Insertion needle (see protocol 2)

Alternate Protocol 1: Catheter Implantation in the Mouse

  • Sterilized mouse catheter (see protocol 1) and cap (see protocol 2)
  • Flushing syringes (see protocol 2): one containing sterile physiological saline and the other containing heparinized (30 USP U/ml) saline with antibiotic, e.g., 33 mg/ml cefazolin
  • Mice

Alternate Protocol 2: Implantation of a Second Self‐Administration Catheter

  Materials
  • Two rat flushing syringes (see protocol 2)
  • Heparinized saline (30 USP U/ml)
  • Catheter test solution: 15 mg/ml ketamine, 0.75 mg/ml midazolam in 0.9% saline

Support Protocol 2: Re‐Position Self‐Administration Catheter

  Materials
  • Two mouse flushing syringes ( protocol 2)
  • Heparinized saline (30 USP U/ml)
  • Catheter test solution: 15 mg/ml ketamine, 0.75 mg/ml midazolam in 0.9% saline
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Figures

Videos

Literature Cited

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