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Vol. 288, Issue 3, 1269-1277, March 1999
Emory University School of Medicine, Department of Pharmacology,
Atlanta, Georgia
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.
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