Self-administration of an enkephalin analog by rhesus monkey

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Abstract

Intravenous injections of a synthetic enkephalin analog, FK-33-824 were found to maintain operant responding under second-order schedule control (FR 4 [VR 16:S]) in five, morphine-dependent rhesus monkeys. All monkeys self-administered enkephalin in amounts equivalent to morphine at comparable doses per injection. Each of five doses of enkephalin (0.5, 0.25, 0.125, 0.05 and 0.01 mg/kg/inj) were substituted for morphine during 10 consecutive sessions over a 56 hr period. No monkey developed opiate withdrawal signs during enkephalin substitution except at the lowest enkephalin dose (0.01 mg/kg/inj). Although the number of enkephalin injections self-administered increased as the dose per injection progressively decreased, there was a significant linear decrease (p<0.05) in mg/kg/enkephalin per session at doses of 0.25 mg/kg/inj and below. Reductions in morphine dose per injection, over a range of 0.5 to 0.125 mg/kg/inj produced comparable increases in number of injections per session, but no significant changes in morphine intake. The number of food pellets earned on a second order FR 4 (VR 16:S) schedule decreased during enkephalin substitution. These decreases were significant at the highest doses of enkephalin (0.5 to 0.125 mg/kg/inj). These data attest to the reinforcing characteristics of an enkephalin analog in rhesus monkey and suggest that natural polypeptides may contribute to the reinforcing properties of opiate drugs.

References (37)

  • S.R. Goldberg

    Comparable behavior maintained under fixed-ratio and second-order schedules of food presentation, cocaine injection or d-amphetamine injection in the squirrel monkey

    J. Pharmac. exp. Thér.

    (1973)
  • S.R. Goldberg et al.

    Second-order schedules of drug injection

  • S.R. Goldberg et al.

    Behavior maintained under a second-order schedule by intramuscular injection of morphine or cocaine in rhesus monkeys

    J. Pharmac. exp. Thér.

    (1976)
  • S.R. Goldberg et al.

    Nalorphine-induced changes in morphine self-administration in rhesus monkeys

    J. Pharmac. exp. Thér

    (1971)
  • A. Goldstein

    Opioid peptides (endorphins) in pituitary and brain

    Science

    (1976)
  • J. Hughes et al.

    Identification of two related pentapeptides from the brain with potent opiate agonist activity

    Nature

    (1975)
  • R.T. Kelleher

    Characteristics of behavior controlled by scheduled injections of drugs

  • R.T. Kelleher et al.

    Schedules using noxious stimuli. III. Responding maintained with response-produced electric shocks

    J. exp. Analysis Behav.

    (1968)
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