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Vol. 290, Issue 3, 1157-1164, September 1999
-Opioid
Agonist SNC80 in Rhesus Monkeys1
Alcohol and Drug Abuse Research Center, Harvard Medical
School-McLean Hospital, Belmont, Massachusetts (M.R.B., S.S.N.,
N.K.M.); and Laboratory of Medicinal Chemistry, National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health, Bethesda, Maryland (M.S.F., X.Z., K.C.R.)
Five rhesus monkeys were trained to discriminate the nonpeptidic,
-opioid agonist SNC80 (0.32 mg/kg i.m.) from saline by using a
food-reinforced drug-discrimination procedure. Cumulative doses of
SNC80 produced a dose-dependent increase in SNC80-appropriate responding and a dose-dependent decrease in response rate. In time-course studies, peak effects of the training dose of SNC80 were
observed after 15 min, and these effects diminished over 240 min. In
substitution studies, other piperazinyl benzamide agonists (SNC86,
SNC162, and SNC243A) substituted for SNC80 with relative potencies
similar those of SNC80. However, SNC67, the (
)-enantiomer of SNC80,
did not occasion SNC80-appropriate responding up to a dose (32.0 mg/kg)
that produced convulsions in one monkey. The µ agonists morphine and
fentanyl and the 
agonists U-50,488 and enadoline failed to
substitute for SNC80 up to doses that eliminated responding. Two
nonopioids (the N-methyl-D-aspartate antagonist ketamine and the monoamine reuptake inhibitor cocaine) also
produced primarily saline-appropriate responding. Both the discriminative stimulus and rate-decreasing effects of SNC80 were antagonized by the -selective antagonist naltrindole (0.01-1.0 mg/kg) but not by doses of the opioid antagonist quadazocine (0.1-1.0 mg/kg) that block the effects of µ and agonists. These data suggest that the discriminative stimulus effects of SNC80 are mediated
by -opioid receptors and that the discriminative stimulus effects
of opioids in primates can be differentiated from the effects of
other opioid and nonopioid compounds.
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