Oral self-administration of triazolam, diazepam and ethanol in the baboon: drug reinforcement and benzodiazepine physical dependence.
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 greater than year without the inducing procedures; drug intake greater than 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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Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224.
Griffiths
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D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D004327:Drinking Behavior / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D005502:Food; D006207:Half-Life; D008297:Male; D010215:Papio; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D019966:Substance-Related Disorders / Q000523:psychology*; D014229:Triazolam / Q000494:pharmacology*
D014229:Triazolam; D000431:Ethanol; D005442:Flumazenil; D003975:Diazepam