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  • Supplementary Materials
    Supplementary Materials Hyporesponsivity to mu-opioid receptor agonism in the Wistar-Kyoto rat model of altered nociceptive responding associated with negative affective state Running title: Effects of mu-opioid receptor agonism in Wistar-Kyoto rats Mehnaz I Ferdousi1,3,4, Patricia Calcagno1,2,3,4, Morgane Clarke1,2,3,4, Sonali Aggarwal1,2,3,4, Connie Sanchez5, Karen L Smith5, David J Eyerman5, John P Kelly1,3,4, Michelle Roche2,3,4, David P Finn1,3,4,* 1Pharmacology and Therapeutics, 2Physiology, School of Medicine, 3Centre for Pain Research and 4Galway Neuroscience Centre, National University of Ireland Galway, Galway, Ireland. 5Alkermes Inc., Waltham, Massachusetts, USA. *Corresponding author: Professor David P Finn, Pharmacology and Therapeutics, School of Medicine, Human Biology Building, National University of Ireland Galway, University Road, Galway, H91 W5P7, Ireland. Tel: +353 (0)91 495280 E-mail: [email protected] S.1. Supplementary methods S.1.1. Elevated plus maze test The elevated plus maze (EPM) test assessed the effects of drug treatment on anxiety-related behaviours in WKY and SD rats. The wooden arena, which was elevated 50 cm above the floor, consisted of central platform (10x10 cm) connecting four arms (50x10 cm each) in the shape of a “plus”. Two arms were enclosed by walls (30 cm high, 25 lux) and the other two arms were without any enclosure (60 lux). On the test day, 5 min after the HPT, rats were removed from the home cage, placed in the centre zone of the maze with their heads facing an open arm, and the behaviours were recorded for 5 min with a video camera positioned on top of the arena.
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  • The Human In. Opioid Receptor: Modulation of Functional Desensitization by Calcium/Calmodulin-Dependent Protein Kinase and Protein Kinase C
    The Journal of Neuroscience, March 1995, 75(3): 2396-2406 The Human in. Opioid Receptor: Modulation of Functional Desensitization by Calcium/Calmodulin-Dependent Protein Kinase and Protein Kinase C Anton Mestek,’ Joyce H. Hurley,’ Leighan S. Bye,’ Andrew D. Campbell,1~2 Yan Chen,’ Mingting Tian,’ Jian Liu,’ Howard Schulman,3 and Lei Yu’ ‘Department of Medical and Molecular Genetics and 21nstitute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202 and 3Depattment of Neurobiology, Stanford University School of Medicine, Stanford, California 94305 Opioids are some of the most efficacious analgesics used macological studies have defined three major types of opioid in humans. Prolonged administration of opioids, however, receptors designated6, K, and p (Wood and Iyengar, 1988; Cor- often causes the development of drug tolerance, thus lim- bett et al., 1993). Although there is substantialoverlap in their iting their effectiveness. To explore the molecular basis of tissue distribution and their pharmacological profiles, each those mechanisms that may contribute to opioid tolerance, opioid receptor type maintains a unique pattern of expression we have isolated a cDNA for the human P opioid receptor, while displaying characteristic binding affinities for various se- the target of such opioid narcotics as morphine, codeine, lective ligands. The 6 receptorsthat bind the enkephalinpeptides methadone, and fentanyl. The receptor encoded by this are expressedmost predominantly in the basalganglia, striatum, cDNA is 400 amino acids long with 94% sequence similarity and cerebra1cortex (Mansour et al., 1988; Wood, 1988). Al- to the rat (r. opioid receptor. Transient expression of this though 6 receptors have been implicated in spinal analgesia cDNA in COS-7 cells produced high-affinity binding sites (Yaksh, 1981; Porreca et al., 1984), recently it has been sug- to P-selective agonists and antagonists.
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    6.- BIBLIOGRAFÍA BIBLIOGRAFÍA Abbott F.V., Franklin K.B., Westbrook R.F. The formalin test: scoring properties of the first and second phases of the pain response in rats. Pain. (1995). 60: 91- 102. Abdelhamid E.E., Sultana M., Portoghese P.S., Takemori A.E. Selective blockage of delta opioid receptors prevents the development of morphine tolerance and dependence in mice. J Pharmacol Exp Ther. (1991). 258: 299-303. Acosta C.G., Lopez H.S. Delta opioid receptor modulation of several voltage- dependent Ca(2+) currents in rat sensory neurons. J Neurosci. (1999). 19: 8337-8348. Adams, J.U., Tallarida, R.J., Geller, E.B., Adler, M.W. Isobolographic Superadditivity detween Delta and Mu Opioid Agonists in the Rat Depends on the Ratio of Compounds, the Mu Agonist and the Analgesic Assay Used. J Pharmacol Exp Ther. (1993). 266: 1261-1267. Aghajanian G.K., Wang Y.Y. Pertussis toxin blocks the outward currents evoked by opiate and alpha 2-agonists in locus coeruleus neurons. Brain Res. (1986). 371: 390-394. Akil H., Madden J., Patrick R.L., Barchas J.D. Stress-induced increase in endogenous opiate peptides; concurrent analgesia and its partial reversal by naloxone. En Koterlitz H.W. (Eds.). Opiates and Endogenous Opioid Peptides, Elsevier, Amsterdam. (1976). 63-70. Akiyama Y., Nishimura M., Suzuki A., Yamamoto M., Kishi F., Kawakami Y. Naloxone increases ventilatory response to hypercapnic hypoxia in healthy adult humans. Am Rev Respir Dis. (1990). 142: 301-305. Albrecht E., Heinrich N., Lorenz D., Baeger I., Samovilova N., Fechner K., Berger H. Influence of continuous levels of fentanyl in rats on the mu-opioid receptor in the central nervous system.
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