Psychopharmacology

, Volume 169, Issue 2, pp 135–140

Self-administration of Δ9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys

Authors

  • Zuzana Justinova
    • Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research ProgramNational Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services
  • Gianluigi Tanda
    • Psychobiology Section, Medications Discovery Research Branch, Intramural Research ProgramNational Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services
  • Godfrey H. Redhi
    • Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research ProgramNational Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services
    • Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research ProgramNational Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services
Original Investigation

DOI: 10.1007/s00213-003-1484-0

Cite this article as:
Justinova, Z., Tanda, G., Redhi, G.H. et al. Psychopharmacology (2003) 169: 135. doi:10.1007/s00213-003-1484-0

Abstract

Rationale

Interest in therapeutic activities of cannabinoids has been restrained by the fact that they are most often mediated through activation of cannabinoid CB1 receptors, the same receptors that mediate the effects of Δ9-tetrahydrocannabinol (THC) and are responsible for the abuse liability of marijuana. Persistent intravenous self-administration of THC by animals was first demonstrated in squirrel monkeys and shown to be mediated by CB1 receptors, but monkeys in the study had a history of cocaine self-administration, raising the possibility that persistent neurobiological adaptations might subsequently predispose animals to self-administer THC.

Objectives

To demonstrate persistent intravenous self-administration of THC in drug-naive squirrel monkeys.

Methods

Monkeys with no history of exposure to other drugs learned to press a lever for intravenous injections (0.2 ml in 0.2 s) of THC under a 10-response, fixed-ratio schedule with a 60-s time-out after each injection. Acquisition of THC self-administration was rapid and the final schedule was reached in 11–34 sessions. Dose of THC was then varied from 1 to 16 µg/kg per injection with vehicle extinction following each dose of THC.

Results

THC maintained significantly higher numbers of self-administered injections per session and higher rates of responding than vehicle at doses of 2, 4 and 8 µg/kg per injection, with maximal rates of responding at 4 µg/kg per injection. Response rates, injections per session and total THC intake per session were two- to three-fold greater in monkeys with no history of exposure to other drugs compared to previous findings in monkeys with a history of cocaine self-administration.

Conclusions

THC can act as an effective reinforcer of drug-taking behavior in monkeys with no history of exposure to other drugs, suggesting that self-administration of THC by monkeys provides a reliable animal model of human marijuana abuse.

Keywords

CannabisΔ9-Tetrahydrocannabinol (THC)Drug self-administrationSquirrel monkeysMarijuana

Copyright information

© Springer-Verlag 2003