kappa-Opioid withdrawal in Planaria.
Many drug-abusers engage in poly-drug abuse, but there has been relatively little quantification of withdrawal from poly-drug use. Planarians are an advantageous model for these studies due to mammalian-relevant neurotransmitter systems (e.g. dopamine, opioid, and 5-HT). We recently developed a metric that quantified an acute cocaine withdrawal phenomenon in planarians. However, despite much indirect evidence, we lacked direct evidence of a receptor- or carrier-mediated effect. We now report dose-related, naloxone- and nor-binaltorphine-sensitive acute abstinence-induced withdrawal and naloxone-precipitated withdrawal from the kappa-opioid agonist U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)-benzeneacetamide). The less active enantiomer [1R,2R]U-50,488 produced significantly less withdrawal and U-50,488H withdrawal was not due to pH or osmolarity. These data provide pharmacologic evidence of a kappa-opioid receptor-mediated withdrawal phenomenon and neuroadaptation to a pharmacologic stimulus (adaptations in transduction mechanisms) in this model.
Raffa
Robert B
RB
Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA. robert.raffa@temple.edu
Stagliano
Gregory W
GW
Umeda
Sumiyo
S
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D009994:Osmolar Concentration; D010932:Planarians / Q000187:drug effects* / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology
D009292:Narcotic Antagonists; D009294:Narcotics; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer