TY - JOUR T1 - Discriminative Stimulus Effects of Naltrexone After a Single Dose of Morphine in the Rat JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1269 LP - 1277 VL - 288 IS - 3 AU - Keith W. Easterling AU - Stephen G. Holtzman Y1 - 1999/03/01 UR - http://jpet.aspetjournals.org/content/288/3/1269.abstract N2 - The discriminative stimulus effects of an acute morphine (MOR) → naltrexone (NTX) combination were characterized and compared with the stimulus effects of NTX-precipitated and spontaneous withdrawal from chronic MOR administration. Adult male Sprague-Dawley rats (n = 6–8) were trained to discriminate between two drug treatments in a discrete-trial avoidance/escape procedure: MOR (10 mg./kg, s.c., 4 h) → NTX (0.3 mg/kg, s.c., 0.25 h) versus saline (SAL, 1 ml/kg, s.c., 4 h) → NTX (0.3 mg/kg, s.c., 0.25 h). Subjects responded only on the SAL → NTX-appropriate lever when SAL was given 3.75 h after MOR or 3.75 h before any dose of NTX (0.3–100 mg/kg). Responding was dose dependent and MOR → NTX-appropriate when NTX (0.01–0.1 mg/kg) followed MOR. Full MOR → NTX-appropriate responding was dependent on the pretreatment dose and time of MOR, with full effects observed only when MOR (10 mg/kg) was given 3 to 4 h before NTX. While subjects were maintained on either 20- or 40 mg/kg/day of MOR via osmotic pump, NTX produced full dose-dependent, MOR → NTX-appropriate responding. When the MOR-filled pumps were removed, partial MOR → NTX-appropriate responding occurred, peaking at 6 to 12 h. The physical withdrawal signs produced by NTX after acute or during chronic MOR exposure were of smaller magnitude compared with the ones that occurred during abrupt withdrawal from chronic MOR. A qualitatively unique “withdrawal” stimulus that is dose- and time-dependent appears to be the basis of this MOR → NTX discrimination. The American Society for Pharmacology and Experimental Therapeutics ER -