Intravenous Self‐Administration Techniques in Monkeys

Donna M. Platt1, Galen Carey2, Roger D. Spealman1

1 New England Primate Research Center Harvard Medical School, Southborough, Massachusetts, 2 MPI Research, Mattawan, Michigan
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.21
DOI:  10.1002/0471142301.ns0921s32
Online Posting Date:  August, 2005
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Abstract

Drug self‐administration is a procedure in which a subject performs a response, called an operant, that results in the delivery of a drug injection. This procedure is viewed as a relevant model for the study of human drug‐taking behavior. Drug self‐administration in primates has several characteristics that resemble drug‐taking behavior in humans, and drugs that are commonly abused by humans also typically maintain self‐administration behavior in monkeys. Drug self‐administration procedures allow for the study of a variety of drug properties. For instance, they are used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of drug addiction. These procedures also can be used to study the process of drug reinforcement. This unit describes intravenous drug self‐administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys.

     
 
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Table of Contents

  • Strategic Planning
  • Basic Protocol 1: Self‐Administration Training and Testing
  • Support Protocol 1: Catheter Implantation
  • Support Protocol 2: Determination of Catheter Patency Using the Methohexital Test
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Self‐Administration Training and Testing

  Materials
  • Monkeys: male/female 4‐ to 5‐kg rhesus macques (Covance Research Products) or 0.75‐ to 1‐kg squirrel monkeys (Worldwide Primates)
  • Raisins or peanuts (optional)
  • Short length of metal chain (optional)
  • 100 to 200 IU/ml heparinized saline, sterile
  • Sterile saline
  • Training compound and vehicle, filter‐sterilized
  • Remote‐chamber or home‐cage self‐administration apparatus (see ) with schedule control apparatus (Med Associates)
  • Tether system: custom‐fitted jacket connected to a flexible stainless steel cable by a fluid swivel (Lomir Biomedical; Alice King Chatham Medical Arts)
  • Restraining chair (for remote chamber only; Plas‐Labs, Crist Instruments, or Primate Products for macques; Med Associates for squirrel monkeys)
  • Additional reagents and equipment for implanting and testing patency of catheter (see Support Protocols protocol 21 and protocol 32)

Support Protocol 1: Catheter Implantation

  • Habituated monkeys (see protocol 1, step )
  • Ketamine, veterinary grade (Henry Schein)
  • Atropine, veterinary grade (Henry Schein)
  • Propofol, veterinary grade (Henry Schein)
  • 1% to 1.5% (v/v) isoflurane in oxygen
  • Povidone iodine (Operand, Henry Schein)
  • 70% (v/v) ethanol
  • Tracheal tube
  • Intravenous catheter line (angiocatheter; 22‐G for macaques, 24‐G for squirrel monkeys)
  • Electric razor
  • Sterile surgical instruments
  • Surgical table
  • 4‐0 Ethibond Excel polyester suture (Ethicon)
  • Vascular clips
  • Vannas scissors
  • Catheter (see Table 9.21.1)
  • Sterile stainless steel obturator (optional)
  • Access port (optional; Access Technologies)
NOTE: Perform catheter implantations under aseptic conditions.

Support Protocol 2: Determination of Catheter Patency Using the Methohexital Test

  Materials
  • Catheterized monkey (see protocol 2)
  • Methohexital solution
  • Sterile saline
  • Three‐way valve to fit catheter
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Figures

Videos

Literature Cited

   Caine, S.B., Lintz, R., and Koob, G.F. 1993. Intravenous drug self‐administration techniques in animals. In Behavioral Neuroscience: A Practical Approach (A. Seghal, ed.) pp. 117‐139. Oxford University Press, New York.
   Goldberg, S.R. 1975. Stimuli associated with drug injections as events that control behavior. Pharmacol. Rev. 27:325‐340.
   Johanson, C.E. 1976. Pharmacological and environmental variables affecting drug preference in rhesus monkeys. Pharmacol. Rev. 27:343‐355.
   Kelleher, R.T. 1975. Characteristics of behavior controlled by scheduled injections of drugs. Pharmacol. Rev. 27:307‐324.
   Nader, M.A. and Mach, R.H. 1996. Self‐administration of the dopamine D3 agonist 7‐OH‐DPAT in rhesus monkeys is modified by prior cocaine exposure. Psychopharmacology Ser. (Berl.) 125:13‐22.
   Negus, S.S. 2003. Rapid assessment of choice between cocaine and food in rhesus monkeys: Effects of environmental manipulations and treatment with d‐amphetamine and flupenthixol. Neuropsychopharmacology 28:919‐931.
   Schuster, C.R. and Johanson, C.E. 1974. The use of animal models for the study of drug abuse. In Research Advances in Alcohol and Drug Problems (R.J. Gibbins, Y. Israel, H. Kalant, R.E. Popham, W. Schmidt, R.G. Smart, eds.) pp 1‐31. John Wiley & Sons, New York.
   Spealman, R.D. and Goldberg, S.R. 1978. Drug self‐administration by laboratory animals: Controls by schedules of reinforcement. Ann. Rev. Pharmacol. Toxicol. 18:313‐339.
   Weeks, J.R. 1972. Long‐term intravenous infusion. In Methods in Psychobiology, Vol. 2 (R.D. Meyers, ed.) pp. 155‐168. Academic Press, New York.
Key References
   Kelleher 1975. See above.
  Description of characteristic performance under different schedules of drug self‐administration.
   Schuster and Johanson, 1974. See above.
  Description of use of drug self‐administration procedures to assess the abuse potential of drugs.
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