TY - JOUR
T1 - Partial generalization in pigeons trained to discriminate morphine from saline
T2 - Applications of receptor theory
AU - Koek, Wouter
AU - Woods, James H.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1989
Y1 - 1989
N2 - In pigeons trained to discriminate 5.6 mg/kg of morphine from saline, cyclazocine, l‐N‐allyl‐normetazocine (l‐NANM, l‐SKF10,047), and ketamine, but not U50,488, produced partial generalization, i.e., a maximum level of drug‐appropriate responding between the levels produced by saline and by the training drug. The generalization gradient of cyclazocine and of l‐NANM, but not that of ketamine, was less steep than the gradient of morphine. Cyclazocine and l‐NANM, but not U50,488 and ketamine, antagonized partially the discriminative stimulus (DS) effects of morphine. Naltrexone antagonized the DS effects of morphine, cyclazocine, and l‐NANM, but not ketamine. Increasing the training dose of morphine shifted the morphine gradient to the right, increased the antagonist effects of cyclazocine and of l‐NANM, and decreased their agonist effects, but did not alter the effects of ketamine. Decreasing the training dose of morphine shifted the morphine gradient to the left and increased the agonist effects of cyclazocine, but did not alter the effects of l‐NANM and ketamine. The full generalization produced by cyclazocine when the training dose of morphine was lowered could be blocked completely by naltrexone and l‐NANM, but not by ketamine. These results suggest that cyclazocine and l‐NANM, but not ketamine, produced partial generalization because of their low efficacy at the receptor that underlies the DS effects of morphine. However, the results obtained with ketamine suggest that partial generalization may also be produced through other mechanisms.
AB - In pigeons trained to discriminate 5.6 mg/kg of morphine from saline, cyclazocine, l‐N‐allyl‐normetazocine (l‐NANM, l‐SKF10,047), and ketamine, but not U50,488, produced partial generalization, i.e., a maximum level of drug‐appropriate responding between the levels produced by saline and by the training drug. The generalization gradient of cyclazocine and of l‐NANM, but not that of ketamine, was less steep than the gradient of morphine. Cyclazocine and l‐NANM, but not U50,488 and ketamine, antagonized partially the discriminative stimulus (DS) effects of morphine. Naltrexone antagonized the DS effects of morphine, cyclazocine, and l‐NANM, but not ketamine. Increasing the training dose of morphine shifted the morphine gradient to the right, increased the antagonist effects of cyclazocine and of l‐NANM, and decreased their agonist effects, but did not alter the effects of ketamine. Decreasing the training dose of morphine shifted the morphine gradient to the left and increased the agonist effects of cyclazocine, but did not alter the effects of l‐NANM and ketamine. The full generalization produced by cyclazocine when the training dose of morphine was lowered could be blocked completely by naltrexone and l‐NANM, but not by ketamine. These results suggest that cyclazocine and l‐NANM, but not ketamine, produced partial generalization because of their low efficacy at the receptor that underlies the DS effects of morphine. However, the results obtained with ketamine suggest that partial generalization may also be produced through other mechanisms.
KW - cyclazocine
KW - drug discrimination
KW - efficacy
KW - ketamine
KW - l‐N‐allylnormetazocine (l‐SKF10,047) U50,488
KW - opioids
KW - partial agonist
KW - phencyclidine
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U2 - 10.1002/ddr.430160211
DO - 10.1002/ddr.430160211
M3 - Article
AN - SCOPUS:0024391875
VL - 16
SP - 169
EP - 181
JO - Drug Development Research
JF - Drug Development Research
SN - 0272-4391
IS - 2-4
ER -