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Oral self-administration of triazolam, diazepam and ethanol in the baboon: drug reinforcement and benzodiazepine physical dependence

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Abstract

Reinforcing and physical dependence-producing effects of oral diazepam and triazolam (0.01–1.28 mg/ml) were studied in four non-water-deprived baboons in daily 2-3-h sessions. Drinking initially was food-induced, but subsequently it was maintained for>year without the inducing procedures; drug intake>10 mg/kg per session was attained. Triazolam and diazepam reinforcement (compared to vehicle) was concluded for only one baboon for each drug under a single-spout procedure and for two baboons for each drug under a two-spout procedure. However, all baboons showed ethanol reinforcement under a two-spout procedure. When a lever-pressing requirement was imposed for each drink (one-spout procedure), ethanol maintained requirements of 128 or 256 responses/drink, and volume of ethanol consumed was greater than vehicle. Neither benzodiazepine maintained lever pressing better than vehicle at any response requirement and drinking was suppressed by requirements of 1–32. Physical dependence to triazolam and diazepam developed after approximately 1 month of daily ingestion, evidenced by a precipitated withdrawal syndrome after injection of the benzodiazepine antagonist flumazenil. A mild spontaneous withdrawal syndrome occurred after substitution of vehicle for triazolam or diazepam. These data indicate a clear dissociation between the reinforcing and physical dependence-producing effects of triazolam and diazepam.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Suite 3000, 21224, Baltimore, MD, USA

    Nancy A. Ator & Roland R. Griffiths

  2. Department of Neuroscience, The Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Suite 3000, 21224, Baltimore, MD, USA

    Roland R. Griffiths

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  1. Nancy A. Ator
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  2. Roland R. Griffiths
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Ator, N.A., Griffiths, R.R. Oral self-administration of triazolam, diazepam and ethanol in the baboon: drug reinforcement and benzodiazepine physical dependence. Psychopharmacology 108, 301–312 (1992). https://doi.org/10.1007/BF02245116

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  • DOI: https://doi.org/10.1007/BF02245116

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