TY - JOUR
T1 - The cocaine-like behavioral effects of meperidine are mediated by activity at the dopamine transporter
AU - Izenwasser, Sari
AU - Newman, Amy Hauck
AU - Cox, Brian M.
AU - Katz, Jonathan L.
N1 - Funding Information:
We thank Earl Shores and Michael Chider for expert technical assistance with the behavioral studies, and Dr. Rik Kline for his assistance with the molecular modeling. Animals used in this study were maintained in facilities fully accredited by the American Association for the Accreditation of Laboratory Animal Care (AAALAC) and all experimentation was conducted in accordance with the guidelines of the Institutional Care and Use Committee of the Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, and the Guide for Care and Use of Laboratory Animals, National Research Council, Department of Health, Education and Welfare, NIH Publication 85-23, revised 1985. The opinions and assertions contained herein are the private ones of the authors and are not to be construed as reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences.
PY - 1996/2/15
Y1 - 1996/2/15
N2 - Meperidine has atypical opioid receptor agonist effects and shares some structural features with the phenyltropane (WIN) analogs of cocaine. In combination with 0.1 mg/kg naltrexone, meperidine produced cocaine-like discriminative stimulus effects in monkeys, whereas morphine was inactive. Both cocaine and meperidine inhibited [3H]dopamine uptake in chopped rat caudate putamen with comparable potencies; meperidine differed from cocaine in that its effects could be characterized as having predominantly a single high-affinity component. Morphine was not active in inhibiting [3H]dopamine uptake, indicating that the effect of meperidine was not via a classic μ-opioid receptor agonist action. Further, meperidine but not morphine displaced [3H]WIN 35,428 (2β-carbomethoxy-3β-(4-fluorophenyl)tropane) binding. These data suggest that the actions of meperidine that are atypical of opioids are due to activity at the dopamine transporter. In addition, meperidine appears to interact predominantly with the high-affinity component of the dopamine transporter, and this high-affinity component may be the site of importance for the production of cocaine's behavioral effects.
AB - Meperidine has atypical opioid receptor agonist effects and shares some structural features with the phenyltropane (WIN) analogs of cocaine. In combination with 0.1 mg/kg naltrexone, meperidine produced cocaine-like discriminative stimulus effects in monkeys, whereas morphine was inactive. Both cocaine and meperidine inhibited [3H]dopamine uptake in chopped rat caudate putamen with comparable potencies; meperidine differed from cocaine in that its effects could be characterized as having predominantly a single high-affinity component. Morphine was not active in inhibiting [3H]dopamine uptake, indicating that the effect of meperidine was not via a classic μ-opioid receptor agonist action. Further, meperidine but not morphine displaced [3H]WIN 35,428 (2β-carbomethoxy-3β-(4-fluorophenyl)tropane) binding. These data suggest that the actions of meperidine that are atypical of opioids are due to activity at the dopamine transporter. In addition, meperidine appears to interact predominantly with the high-affinity component of the dopamine transporter, and this high-affinity component may be the site of importance for the production of cocaine's behavioral effects.
KW - Cocaine
KW - Dopamine transporter
KW - Meperidine
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U2 - 10.1016/0014-2999(95)00696-6
DO - 10.1016/0014-2999(95)00696-6
M3 - Article
C2 - 8851160
AN - SCOPUS:0030021764
VL - 297
SP - 9
EP - 17
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-2
ER -