Abstract
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.
Footnotes
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Send reprint requests to: Dr. Keith W. Easterling, Emory University, Department of Pharmacology, Atlanta, GA 30322. E-mail:keaster{at}emory.edu
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↵1 Supported in part by National Institutes of Health Grant DA00541 and Research Scientist Award K05DA00008 to S.G.H. Portions of the data were presented at the 1997 annual meeting of the College on Problems of Drug Dependence (Nashville, TN) and the 1997 annual meeting of the Society for the Stimulus Properties of Drugs (New Orleans, LA).
- Abbreviations:
- MOR
- morphine
- NX
- naloxone
- NTX
- naltrexone
- Received June 4, 1998.
- Accepted October 5, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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