TY - JOUR
T1 - Discriminative stimulus effects of BW373U86
T2 - A nonpeptide ligand with selectivity for delta opioid receptors
AU - Comer, S. D.
AU - McNutt, R. W.
AU - Chang, K. J.
AU - De Costa, B. R.
AU - Mosberg, H. I.
AU - Woods, J. H.
PY - 1993
Y1 - 1993
N2 - Several opioid agonists were evaluated in pigeons trained to discriminate i.m. injections of sterile water from either the mu agonist morphine (5.6 mg/kg), the kappa agonist bremazocine (0.032 mg/kg) or (±)-4-((α-R*)-α- ((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N- diethylbenzamide (BW373U86; 0.56 mg/kg). Pigeons were trained to peck one of two keys on a fixed-ratio 20 schedule for food reinforcement. The pattern of substitution of mu, kappa and delta selective agonists in the three groups of birds suggested that the discriminative stimulus effects of morphine, bremazocine and BW373U86 were different; however, a component of the discriminative stimulus effects of BW373U86 appeared to be shared with morphine. Apparent pA2 values for naltrexone with morphine, bremazocine and BW373U86 were 7.6, 6.8 and 6.3, respectively. The apparent pA2 value for naltrindole with BW373U86 was 8.3. Naltrindole (10.0 mg/kg) produced a 3- fold shift to the right in the dose-effect curve for morphine but did not antagonize bremazocine. Although results from the substitution experiments suggested that a component of the BW373U86 discriminative stimulus was mediated through mu opioid receptors, the fact that naltrindole was 1000- fold more potent and naltrexone was 30-fold less potent in antagonizing BW373U86 than morphine indicated that the discriminative effects of BW373U86 were also mediated through delta opioid receptors.
AB - Several opioid agonists were evaluated in pigeons trained to discriminate i.m. injections of sterile water from either the mu agonist morphine (5.6 mg/kg), the kappa agonist bremazocine (0.032 mg/kg) or (±)-4-((α-R*)-α- ((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N- diethylbenzamide (BW373U86; 0.56 mg/kg). Pigeons were trained to peck one of two keys on a fixed-ratio 20 schedule for food reinforcement. The pattern of substitution of mu, kappa and delta selective agonists in the three groups of birds suggested that the discriminative stimulus effects of morphine, bremazocine and BW373U86 were different; however, a component of the discriminative stimulus effects of BW373U86 appeared to be shared with morphine. Apparent pA2 values for naltrexone with morphine, bremazocine and BW373U86 were 7.6, 6.8 and 6.3, respectively. The apparent pA2 value for naltrindole with BW373U86 was 8.3. Naltrindole (10.0 mg/kg) produced a 3- fold shift to the right in the dose-effect curve for morphine but did not antagonize bremazocine. Although results from the substitution experiments suggested that a component of the BW373U86 discriminative stimulus was mediated through mu opioid receptors, the fact that naltrindole was 1000- fold more potent and naltrexone was 30-fold less potent in antagonizing BW373U86 than morphine indicated that the discriminative effects of BW373U86 were also mediated through delta opioid receptors.
UR - http://www.scopus.com/inward/record.url?scp=0027495924&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027495924&partnerID=8YFLogxK
M3 - Article
C2 - 8246161
AN - SCOPUS:0027495924
VL - 267
SP - 866
EP - 874
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 2
ER -