SelfAdministration of Cocaine in Naive Rhesus Macaque

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Self-Administration of Cocaine in Naive Rhesus
Macaque

• Jennifer Thompson
• Mentor William Woolverton, Ph.D.

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Cocaine Addiction

• National survey on Drug Abuse and Health 2002
• In 1997, an estimated 1.2 million (0.7
  population) Americans age 12 and older were
  chronic cocaine users
• Office of Drug Control estimates there are 3.5
  million chronic users today
• Adults 18 to 25 years old have a higher rate of
  current cocaine use than those in any other age
  group. Overall, men have a higher rate of current
  cocaine use than do women. Also, according to the
  1997 NHSDA, rates of current cocaine use were 1.4
  percent for African Americans, 0.8 percent for
  Hispanics, and 0.6 percent for Caucasians.
• The 1998 Monitoring the Future Survey, which
  annually surveys teen attitudes and recent drug
  use, reports that lifetime and past-year use of
  crack increased among eighth graders to its
  highest levels since 1991, the first year data
  were available for this grade. The percentage of
  eighth graders reporting crack use at least once
  in their lives increased from 2.7 percent in 1997
  to 3.2 percent in 1998. Past-year use of crack
  also rose slightly among this group, although no
  changes were found for other grades.

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D1 (D1 and D5) and D2 (D2,D3,D4) type receptors
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Potency and Efficacy of Cocaine and their
relationship to abuse

• Potency as a reinforcer?
• Efficacy as a reinforcer?
• What determines abuse in humans?
• Pharmacokinetics rate of cocaine delivery and
  binding
• Balster and Schuster, 1973
• Pharmacodynamics selectivity of a drug
• Pettit and Justice, 1989

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BF Skinner (1904-1990)

• Operant Conditioning
• Reinforcing stimulus
• Extinction
• Schedules of reinforcement
• Continuous reinforcement
• Fixed ratio schedule
• Fixed interval schedule
• Variable schedules
• Progressive ratio

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• Shaping a behavior
• Skinner Box

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Behavior modification

• Extinction of an undesirable behavior by removing
  the reinforcer and replacing it with a desirable
  behavior by reinforcement
• Addiction
• Cocaine analogs

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Behavioral study of cocaine using Rhesus Macaque
(Macaca mulatta)

• Cheek pouches
• Avg. body mass 6 kg.
• Genitals and buttocks reddish color
• Diurnal
• Arboreal and terrestrial
• Visual communication
• Lip retraction to show teeth
• Staring with open mouth
• Tail erect
• lipsmacking

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Monty Rhesus Macaque 97R0111

• Left Brachial
• implanted

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• Cubicle of 1.0m x 1.0m x 1.0m
• Stainless steel harness with tether
• Front door of cubicle is clear plastic
• Two response levers mounted on plastic door with
  four stimulus
• two white above each lever
• Unlimited access to water
• 10 biscuits monkey chow/day
• Fresh fruit daily
• Vitamin supplement 3x/week
• Light cycle 16hrs.light/8hrs.dark

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• Naive to cocaine
• Just finished Fixed-ratio study 5/16/04
• Shaping behavior begun 5/20/04
• Alternating cocaine
• 0.1mg/kg/injection and saline
• Pump speed 1.24 ml/10s
• Weight
• 5/3 7.4 kg
• 5/18 7.9 kg
• 7/27 9.75 kg

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• Test sessions began 6/20/04
• saline test sessions began after shaping
  behavior responses were stable
• Stable
• Minimum 18-20 injections/session of
  0.1mg/kg/injection cocaine
• Maximum 0-4 injections/session of saline
• Tested different potencies of cocaine to
  determine efficacy
• Test Sessions
• cocaine 0.1 mg/kg/injection
• (stable of injections)
• test session
• saline
• cocaine 0.1 mg/kg/injection
• (stable of injections)
• test session.

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Many Thanks!

• William Woolverton, Ph.D.
• Sunmee Wee
• Hamilton McGee
• Christine Tiep
• Mary Cox
• Woolverton Lab
• Dr. Paul
• Tracie Findley

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Works Cited
National Institute on Drug Abuse and Research
(2002) http//www.drugabuse.gov/ResearchReports/C
ocaine/cocaine2.ht Balster RL, Schuster CR
(1973) Fixed-interval schedule of cocaine
reinforcementL effect of dose and infusion
duration. J Exp Animal Behavior 20
(1)119-129 Pettit HO, Justice JB Jr. (1989).
Dopamine in the nucleus accumbens during cocain
self-administration as studied by in vivo
microdialysis. Pharmacol Biochem Behav 34(4)L
899-904