TY - JOUR
T1 - Pharmacological selectivity of CTAP in a warm water tail-withdrawal antinociception assay in rats
AU - Steinmiller, Caren L.
AU - Young, Alice M.
N1 - Funding Information:
Acknowledgments The authors thank Susan Irtenkauf, John Mor-etti, and Ross Witte for technical assistance. The scientific suggestions of Drs. Scott Bowen and Marianne Evola are greatly appreciated. This work was supported by US Public Health Service Grant DA03796.
PY - 2008/1
Y1 - 2008/1
N2 - Rationale: To facilitate in vivo characterization of the mu antagonist Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), the present study characterized CTAP selectivity in vivo. Objectives: CTAP, the classical antagonist naltrexone, the kappa-selective antagonist nor-binaltorphimine (BNI), and the delta-selective antagonist naltrindole were compared as antagonists of representative mu, kappa, and delta agonists in a warm water tail-withdrawal assay. Materials and methods: Male Sprague-Dawley rats were pretreated with CTAP (0.01 to 10.0 μg, i.c.v.), naltrexone (0.1 to 10 mg/kg s.c.; 0.1 to 10 μg i.c.v.), nor-BNI (1 mg/kg s.c.), or naltrindole (0.01 to 1 μg, i.c.v.) and tested with cumulative doses of agonist in 50 or 55°C tail-withdrawal assays. Results: At 55°C, morphine and DAMGO produced dose-dependent antinociceptive effects that were antagonized by CTAP or naltrexone (s.c. or i.c.v.) in a surmountable, dose-dependent manner. Neither kappa agonists (bremazocine, spiradoline, U69,593; all s.c.) nor the delta agonist DPDPE (i.c.v.) produced antinociception at 55°C, but all produced full antinociception at 50°C. CTAP did not antagonize effects of spiradoline, U69,593, or DPDPE, whereas nor-BNI produced insurmountable antagonism of effects of kappa agonists, and naltrindole produced surmountable antagonism of effects of DPDPE. Apparent pA 2 estimates for naltrexone, CTAP, and naltrindole agreed with published estimates, although Schild slopes diverged from predictions for simple competitive antagonism. Conclusions: CTAP produces dose-dependent antagonism selective for mu-agonist effects in a standard 55°C tail withdrawal antinociceptive assay.
AB - Rationale: To facilitate in vivo characterization of the mu antagonist Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), the present study characterized CTAP selectivity in vivo. Objectives: CTAP, the classical antagonist naltrexone, the kappa-selective antagonist nor-binaltorphimine (BNI), and the delta-selective antagonist naltrindole were compared as antagonists of representative mu, kappa, and delta agonists in a warm water tail-withdrawal assay. Materials and methods: Male Sprague-Dawley rats were pretreated with CTAP (0.01 to 10.0 μg, i.c.v.), naltrexone (0.1 to 10 mg/kg s.c.; 0.1 to 10 μg i.c.v.), nor-BNI (1 mg/kg s.c.), or naltrindole (0.01 to 1 μg, i.c.v.) and tested with cumulative doses of agonist in 50 or 55°C tail-withdrawal assays. Results: At 55°C, morphine and DAMGO produced dose-dependent antinociceptive effects that were antagonized by CTAP or naltrexone (s.c. or i.c.v.) in a surmountable, dose-dependent manner. Neither kappa agonists (bremazocine, spiradoline, U69,593; all s.c.) nor the delta agonist DPDPE (i.c.v.) produced antinociception at 55°C, but all produced full antinociception at 50°C. CTAP did not antagonize effects of spiradoline, U69,593, or DPDPE, whereas nor-BNI produced insurmountable antagonism of effects of kappa agonists, and naltrindole produced surmountable antagonism of effects of DPDPE. Apparent pA 2 estimates for naltrexone, CTAP, and naltrindole agreed with published estimates, although Schild slopes diverged from predictions for simple competitive antagonism. Conclusions: CTAP produces dose-dependent antagonism selective for mu-agonist effects in a standard 55°C tail withdrawal antinociceptive assay.
KW - Antinociception
KW - CTAP selective drug antagonism
KW - Opioid analgesics
UR - http://www.scopus.com/inward/record.url?scp=36348974677&partnerID=8YFLogxK
U2 - 10.1007/s00213-007-0898-5
DO - 10.1007/s00213-007-0898-5
M3 - Article
C2 - 17882404
AN - SCOPUS:36348974677
VL - 195
SP - 497
EP - 507
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 4
ER -