A quantitative assessment of phencyclidine dependence produced by oral self-administration in rhesus monkeys

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Abstract

Three rhesus monkeys were trained to self-administer orally delivered phencyclidine (PCP) and water under concurrent fixed-ratio schedules. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts. PCP deliveries exceeded water deliveries throughout the experiment, indicating that the drug was functioning as a positive reinforcer. The monkeys were also trained to lever press under a fixed-ratio 64 or fixed-ratio 80 schedule of food delivery. Food was available during three 1 hr periods each day, with 6.5 hr of liquid availability between each food component. After behavior stabilized for at least 10 days under these conditions, water was substituted for PCP for 2, 4, 8 or 24 days. Food-maintained responding was severely disrupted for the first 2 days of water substitution, with a steady recovery over the following 6 days. The monkeys were noticeably irritable during water substitution, but there were no other physical signs of PCP withdrawal. Disruptions in food-maintained responding were immediately reversed when PCP was reinstated. Subsequently, the PCP concentration was varied (0.062, 0.125, 0.25, 0.5 and 1 mg/ml), and PCP intake (milligrams per kilogram), as well as the magnitude of disruptions in pellet deliveries (upon termination of PCP access), also varied directly with PCP intake. The amount of PCP intake was also altered by limiting PCP (0.25 mg/ml) access to every 2nd or 4th day, with water available on intervening days. Pellet deliveries were substantially disrupted during water substitution, and food-maintained responding immediately returned to control levels when PCP became available. Reduction in the amount of daily access to PCP from 19.5 to 3 to 1 hr also resulted in systematic reductions in disruptions in food-reinforced responding during PCP withdrawal. Throughout the experiment, withdrawal disruptions were replicated many times; however, there was no evidence of tolerance or sensitivity to these behavioral effects. The methods used in the present study provide a sensitive quantitative assessment of severe and prolonged behavioral disruptions resulting from termination of both continuous and intermittent PCP-reinforced behavior.

Original languageEnglish (US)
Pages (from-to)405-412
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume242
Issue number2
StatePublished - 1987

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