Schedule-induced oral narcotic self-administration: acute and chronic effects

Abstract

A pattern of lever pressing was maintained in rats by presenting a food pellet following the first lever press to occur after at least 90-seconds had elapsed (fixed-interval 90-second schedule of food presentation, FI 90-second). With a drinking solution available, a pattern of excessive postpellet drinking (schedule-induced polydipsia) developed and was used to induce rats to drink solutions containing varying concentrations of narcotics. During acute exposure to morphine HCl, morphine SO4 or methadone HCl in the drinking solution, drinking decreased as a function of increasing drug concentration (from 0.3-1 mg/ml), but the total dose of narcotic ingested increased as a function of increasing drug concentration. The highest average dose of morphine HCl consumed in tap water was 30 mg/kg within an hour session. When morphine HCl was presented in an isotonic saline solution, drinking was increased and the highest average dose of morphine HCl ingested was 60 mg/kg within an hour session. The use of an isotonic saline solution did not appreceiably enhance the ingestion methadone HCl (about 30 mg/kg/hr). After chronic exposure to drug solutions for daily 4-hour sessions, the doses ingested averaged between 150 and 250 mg/kg/4 hr for 1 mg/ml solutions of morphine HCl and morphine SO4. The stable pattern of drinking exhibited by rats on the 0.5 mg/ml morphine HCl solution was characterized by a dissociation of drinking from pellet presentation. Chronic exposure to methadone HCl solutions (1 mg/ml) produced less drinking and lower doses ingested (approximately 100 mg/kg) than was obtained with either morphine HCl or morphine SO4 at an equal concentration.