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Evaluation of a suspension system for intra venous self administration studies of water insoluble compounds in the rhesus monkey



Evaluation of a suspension system for intra venous self administration studies of water insoluble compounds in the rhesus monkey



Pharmacology Biochemistry and Behavior 7(4): 357-364



A suspension system for water-insoluble drugs was evaluated using the mouse tail-flick test for analgesia and schedule-controlled responding in rhesus monkeys. One group of monkeys was trained to respond for food reinforcement under a chain fixed-interval 9 min fixed-ratio 10 schedule of reinforcement (chain FI-FR). Another group was trained to respond for intravenous cocaine injections (100 .mu.g/kg/inj) under an FR-10 schedule. Water-insoluble compounds were suspended in emulphor:ethanol:saline. The bioavailability of these drug suspensions was found to be equivalent to water-soluble compounds by comparing the activity of the water-soluble and water-insoluble salts of (+)-propoxyphene in the mouse tail-flick test. The behavioral effects of these drug suspensions were also determined in the group of monkeys which was trained to respond for food under the chain FI-FR schedule. Dose-related decreases in responding were produced by (+)-propoxyphene HCl (water-soluble), (+)-propoxyphene napsylate (water-insoluble) and a cannabinoid, (.+-.)-9-nor-9.beta.-OH-hexahydrocannabinol (.beta.-HHC) (water insoluble). Doses of (+)-propoxyphene HCl (in saline) and (+)-propoxyphene napsylate (in the emulphor suspension system) were equally effective in disrupting food-reinforced responding and in reinforcing self-administration behavior in rhesus monkeys. .beta.-HHC was more potent than (+)-propoxyphene in disrupting food-reinforced responding but failed to maintain self-administration behavior. Drug reinforcement of self-administration behavior is correlated to likelihood of human abuse.

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Accession: 005395766

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PMID: 928494



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