title: The kappa-opioid receptor antagonist nor-BNI inhibits cocaine and amphetamine, but not cannabinoid (WIN 52212-2), abstinence-induced withdrawal in planarians: an instance of 'pharmacologic congruence'.
abstract: The broad applicability of receptor theory to diverse species, from invertebrates to mammals, provides evidence for the evolution in complexity of pharmacologic receptor diversification and of receptor-effector signal transduction mechanisms. However, pre-mammalian species have less receptor subtype differentiation, and thus, might share signal transduction pathways to a greater extent than do mammals, a phenomenon that we term 'pharmacologic congruence'. We have demonstrated previously that the lowest species considered to have a centralized nervous system, planarians, display both abstinence-induced and antagonist-precipitated withdrawal signs, indicative of the development of physical dependence. We report here: (1) amphetamine abstinence-induced withdrawal, and (2) the attenuation of cocaine and amphetamine, but not cannabinoid agonist (WIN 52212-2), abstinence-induced withdrawal by the opioid receptor antagonist naloxone and by the selective kappa-opioid receptor subtype antagonist nor-BNI (nor-Binaltorphimine), but not by the selective mu-opioid or the delta-opioid receptor subtype antagonists CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)) and naltrindole. These results provide evidence that the withdrawal from cocaine and amphetamine, but not cannabinoids, in planarians is mediated through a common nor-BNI-sensitive (kappa-opioid receptor-like) pathway.
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA. robert.raffa@temple.edu
authors.forename: Robert B
authors.initials: RB
authors.lastname: Raffa
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Stagliano
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Ross
authors.forename: Jenay A
authors.initials: JA
authors.lastname: Powell
authors.forename: Austin G
authors.initials: AG
authors.lastname: Phillips
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ding
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
mesh_terms: D000661:Amphetamine / Q000009:adverse effects*; D000700:Analgesics / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines / Q000009:adverse effects; D003042:Cocaine / Q000009:adverse effects*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D004347:Drug Interactions; D009025:Morpholines / Q000009:adverse effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009281:Naphthalenes / Q000009:adverse effects; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010932:Planarians; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D018765:Dopamine Uptake Inhibitors; D009025:Morpholines; D009281:Naphthalenes; D009292:Narcotic Antagonists; C051844:norbinaltorphimine; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009271:Naltrexone; D000661:Amphetamine; D003042:Cocaine