References on the Administration of Naloxone and Naltrexone Using ALZET® Osmotic Pumps

1. Naloxone

16203 Lockie, S. H., Stefanidis, A., Tschop, M. H., Oldfield, B. J. Combination cannabinoid and opioid receptor antagonists improves metabolic outcomes in obese mice. Mol Cell Endocrinol 2015; 417(--):10-19. >>> Naloxone; Saline, normal; SC; mice; 1007D; Controls received mp w/ vehicle; animal info: obesity induced, C57black/6J male mice, 6 wks old; functionality of mp verified by behavioral test; dose-response (pg 13, 14); dose-response (pg 13, 14); behavioral testing (Porsolt forced swim, Elevated Plus Maze, Dowel Gnawing); delayed delivery (24 hours via a 1.5 cm vinyl catheter); Isoflurane anesthesia used; minipump combined with a dose of 1 mg/kg/day of rimonabant (rim nal) injected IP; Dose: 0.5 mg/mouse/day.

14250 Kramer, P.R., Umorin, M., Bellinger, L.L., Kramer, P.R. Attenuation of myogenic orofacial nociception and mechanical hypersensitivity by viral mediated enkephalin overproduction in male and female rats. BMC Neurology 2015; 15(--):U1-U12. >>> Naloxone methiodide; naloxone; Saline; SC; Rat; 2002; Controls received mp w/ vehicle; animal info (Sprague Dawley, 280-300g); behavioral testing (von Frey filament);.

13740 Chou, K.Y., Tsai, R.Y., Tsai, W.Y., Wu, C.T., Yeh, C.C., Cherng, C.H., Wong, C.S. Ultra-low dose (+)-naloxone restores the thermal threshold of morphine tolerant rats. Journal of the Formosan Medical Association 2013; 112(-12-):795-800. >>> Morphone; naloxone; Saline; CSF/CNS (intrathecal); Rat; Controls received mp w/ vehicle; animal info (male, Wistar, 350-400g); behavioral testing (tail-flick); dependence; IT catheter created from PE tube joined with silastic tube with epoxy resin and silicon rubber;.

12873 Sato, K.L., King, E.W., Johanek, L.M., Sluka, K.A. Spinal cord stimulation reduces hypersensitivity through activation of opioid receptors in a frequency-dependent manner. EUROPEAN JOURNAL OF PAIN 2013; 17(-4-):551-561. >>> Naloxone; naltrindole; Saline; SC; Rat; 1007D; Control animals received mp w/ vehicle; animal info (Sprague Dawley, 250-350 g).

12095 Hathway, G.J., Vega-Avelaira, D., Fitzgerald, M. A critical period in the supraspinal control of pain: Opioid-dependent changes in brainstem rostroventral medulla function in preadolescence. Pain 2012; 153(-4-):775-783. >>> Naloxone hydrochloride; naloxone methiodide; morphine sulfate; SC; Rat; 2001; Controls received mp w/ saline; animal info (Sprague Dawley, 200-250 g, P7, P14, P21, P28).

11766 Rahim, R.T., Meissler, J.J., Cowan, A., Rogers, T.J., Geller, E., Gaughan, J., Adler, M.W., Eisenstein, T.K. Administration of mu-, kappa- or delta -receptor agonists via 2 osmotic minipumps suppresses murine splenic antibody responses. INTERNATIONAL IMMUNOPHARMACOLOGY 2001; 1(--):2001-2009. >>> Morphine sulfate; U50,488H; DPDPE; naltriben methanesulfonate; deltorphin II; naloxone; Sodium chloride; DMSO; saline, sterile; SC; Mice; 1003D; Controls received mp w/ saline; animal info (6 wks old, pathogen free, C3HeBrFeJ); comparison of pellets vs. mp; multiple pumps per animal (2);"Minipumps have two advantages, (1) a variety of agonists and antagonists can be used that are not available in slow-release pellet form, and (2) full dose-response curves can be generated."pg 2002;"Minipumps have an advantage over slow-release pellets in that they do not result in splenic atrophy. Thus, drugs administered by the minipumps appear to be less potent, but also to have fewer side effects, than morphine given by slow-release pellets."pg 2007;"The use of osmotic minipumps should permit more extensive and definitive testing of the pharmacokinetics and pharmacodynamic action of a variety of opioids for their effects on immune cell function."pg 2008; 10% DMSO used.

11759 Lockie, S.H., Czyzyk, T.A., Chaudhary, N., Perez-Tilve, D., Woods, S.C., Oldfield, B.J., Statnick, M.A., Tschoep, M.H. CNS Opioid Signaling Separates Cannabinoid Receptor 1-Mediated Effects on Body Weight and Mood-Related Behavior in Mice. Endocrinology 2011; 152(-10-):3661-3667. >>> Naloxone; binaltorphimine, nor; CSF/CNS; Mice; 1007D; Animal info (129/SvEv, lacking MOR, KOR, DOR); ALZET brain infusion kit 3 used; cyanoacrylate adhesive used; post op. care (meloxiocam); cannula placement verified at end of experiment by methylene blue staining; half-life"Naloxone... has a short half-life in vivo";"NorBNI has... an extremely long half-life"pg 3662.

11712 Peart, J.N., Hoe, L.E.S., Gross, G.J., Headrick, J.P. Sustained Ligand-Activated Preconditioning via delta-Opioid Receptors. Journal of Pharmacology and Experimental Therapeutics 2011; 336(-1-):274-281. >>> Naloxone; BW373U86; U50,488H; morphine-6-glucuronide; morphine-3-glucuronide; wortmannin; PKI-(14-22)-amide; SC; Mice; 1007D; Animal info (7-12 wks old, C57/BL6, male);BW373U86 also known as ()-4-[(R)--[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-hydroxy-hydroxybenzyl]-N,N-diethylbenzamide is a delta opioid receptor selective agonist; U50,488H also known as trans-()-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidin)cyclohexyl)-benzeneacetamide methane sulfonate hydrate is a kappa opioid selective receptor agonist.

11481 Lin, S.L., Tsai, R.Y., Shen, C.H., Lin, F.H., Wang, J.J., Hsin, S.T., Wong, C.S. Co-administration of ultra-low dose naloxone attenuates morphine tolerance in rats via attenuation of NMDA receptor neurotransmission and suppression of neuroinflammation in the spinal cords. Pharmacology Biochemistry and Behavior 2010; 96(-2-):236-245. >>> Morphine; naloxone; CSF/CNS (intrathecal); Rat; Controls received mp w/ saline; animal info (pathogen-free, male, Wistar, 350-400 g); infusion rate of 1 ul/hr; two catheters inserted intrathecally.

11160 Hutchinson, M.R., Zhang, Y.N., Shridhar, M., Evans, J.H., Buchanan, M.M., Zhao, T.X., Slivka, P.F., Coats, B.D., Rezvani, N., Wieseler, J., Hughes, T.S., Landgraf, K.E., Chan, S., Fong, S., Phipps, S., Falke, J.J., Leinwand, L.A., Maier, S.F., Yin, H., Rice, K.C., Watkins, L.R. Evidence that opioids may have toll-like receptor 4 and MD-2 effects. BRAIN BEHAVIOR AND IMMUNITY 2010; 24(-1-):83-95. >>> Morphine; naloxone; SC; Rat; Controls received mp w/ saline; animal info (adult, male, Sprague Dawley, 300-375 g); multiple pumps per animal (2).

10997 Horvath, R.J., Romero-Sandoval, E.A., De Leo, J.A. Inhibition of microglial P2X(4) receptors attenuates morphine tolerance, Iba1, GFAP andμ opioid receptor protein expression while enhancing perivascular microglial ED2. Pain 2010; 150(-3-):401-413. >>> Morphine sulfate; naloxone; SC; Rat; 2ML1; Controls received mp w/ saline; animal info (male, Sprague-Dawley, 175-200 g); one pump contained morphine plus naloxone;"All morphine pumps were filled with 0.833 mg/kg/hr morphine to deliver the equivalent of twice daily 10 mg/kg injections over the course of 24 h"pg 402; tolerance.

10151 Lin, S.L., Tsai, R.Y., Tai, Y.H., Cherng, C.H., Wu, C.T., Yeh, C.C., Wong, C.S. Ultra-low dose naloxone upregulates interleukin-10 expression and suppresses neuroinflammation in morphine-tolerant rat spinal cords. Behavioural Brain Research 2010; 207(-1-):30-36. >>> Naloxone; morphine; CSF/CNS (intrathecal); Rat; Controls received mp w/saline; animal info (male, Wistar, 350-400 g); pumps contained morphine alone or morphine and naloxone; two intrathecal catheters implanted.

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2. Naltrexone

15773 Lara S. Hwa, Akiko Shimamoto, Tala Kayyali, Kevin J. Norman, Rita J. Valentino, Joseph F. DeBold, Klaus A. Miczek. Dissociation of u-opioid receptor and CRF-R1 antagonist effects on escalated ethanol consumption and mPFC serotonin in C57BL/6J mice. Addiction Biology 2016; 21(--):111-124. >>> CP154526; naltrexone; DMSO; CSF, artificial; CSF/CNS; Mice; 1002; Controls received mp w/ vehicle; animal info (male, C58BL/6J, 8 weeks old); functionality of mp verified by IAA drinking test or morphine-sensitive tail withdrawal; ALZET brain infusion kit 3 used; 4% DMSO used; Cannula placement verified via Nissl staining;.

13377 Gibbons, C.R., Liu, S.L., Zhang, Y.M., Sayre, C.L., Levitch, B.R., Moehlmann, S.B., Shirachi, D.Y., Quock, R.M. Involvement of brain opioid receptors in the anti-allodynic effect of hyperbaric oxygen in rats with sciatic nerve crush-induced neuropathic pain. Brain Research 2013; 1537(-;-):111-116. >>> Naltrexone HCl; Saline; CSF/CNS; Rat; 1007D; Animal info (male, Sprague Dawley, albino, 160-180g); ALZET brain infusion kit used; post op. care (ampicillin 100 mg/kg IM; meloxicam 2.0 mg/kg IM); behavioral testing (flexion reflex, flinch response, mechanical threshold pressure); Incision closed with wound clip.

12826 Theberge, F.R., Li, X., Kambhampati, S., Pickens, C.L., Laurent, R.S., Bossert, J.M., Baumann, M.H., Hutchinson, M.R., Rice, K.C., Watkins, L.R., Shaham, Y. Effect of Chronic. Delivery of the Toll-like Receptor 4 Antagonist (+)-Naltrexone on Incubation of Heroin Craving. Biological Psychiatry 2013; 73(-8-):729-737. >>> Naltrexone; Water, sterile; SC; Rat; Control animals received mp w/ vehicle; 14-day pump used.

12084 Vadizan, E.M., Diaz, A., Pilar-Cuellar, F., Lantero, A., Mostany, R., Villar, A.V., Laorden, M.L., Hurle, M.A. Chronic treatment with the opioid antagonist naltrexone favours the coupling of spinal cord mu-opioid receptors to G-alphaz protein subunits. Neuropharmacology 2012; 62(-2-):757-764. >>> Naltrexone; SC; Rat; 2001; Controls received mp w/ saline; animal info (Sprague Dawley, male, 250-300 g).

11848 Chung, E., Zelinski, L.M., Ohgami, Y., Shirachi, D.Y., Quock, R.M. Hyperbaric Oxygen Treatment Induces a 2-Phase Antinociceptive Response of Unusually Long Duration in Mice. JOURNAL OF PAIN 2010; 11(-9-):847-853. >>> L-NAME; naltrexone; Saline, physiological; CSF/CNS; Mice; 2001; Controls received mp w/ vehicle; animal info (NIH, Swiss, 18-22 g); ALZET brain infusion kit used; hyperbaric oxygen.

11815 Fitting, S., Xu, R.Q., Bull, C., Buch, S.K., El-Hage, N., Nath, A., Knapp, P.E., Hauser, K.F. Interactive Comorbidity between Opioid Drug Abuse and HIV-1 Tat Chronic Exposure Augments Spine Loss and Sublethal Dendritic Pathology in Striatal Neurons. American Journal of Pathology 2010; 177(-3-):1397-1410. >>> Naltrexone; DMSO; saline, sterile; SC; Mice; 1007D; Controls received mp w/ vehicle; animal info (HIV-1, TAT, adult, 2-6 mo old); 50% DMSO used.

10974 Stagg, N.J., Mata, H.P., Ibrahim, M.M., Henriksen, E.J., Porreca, F., Vanderah, T.W., Malan, TP Jr. Regular Exercise Reverses Sensory Hypersensitivity in a Rat Neuropathic Pain Model Role of Endogenous Opioids. Anesthesiology 2011; 114(-4-):940-948. >>> Naltrexone; Saline; SC; Rat; 2006; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 250-380 g); wound clips used; neuropathic pain.

10946 Mathew, B., Lennon, F.E., Siegler, J., Mirzapoiazova, T., Mambetsariev, N., Sammani, S., Gerhold, L.M., LaRiviere, P.J., Chen, C.T., Garcia, J.G.N., Salgia, R., Moss, J., Singleton, P.A. The Novel Role of the Mu Opioid Receptor in Lung Cancer Progression: A Laboratory Investigation. Anesthesia and Analgesia 2011; 112(-3-):558-567. >>> Naltrexone, methyl; SC; Mice; 1002; Controls received mp w/ PBS; animal info (MOR KO, C57BL/6 wt); cancer (lung); Methylnaltrexone (also known as MNTX) is a mu opioid receptor inhibitor.

10208 Hill, K.G., Sable, H.J.K., Ferraro, FM III, Kiefer, S.W. Chronic Naltrexone Treatment and Ethanol Responsivity in Outbred Rats. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 2010; 34(-2-):272-279. >>> Naltrexone HCl; Saline, physiological; SC; Rat; 2ML4; Controls received mp w/vehicle; dependence; animal info (male, Long-Evans, 250 g); dose-response (fig .1).

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“All the rats survived for the length of the experiments. The intratracheal pump was well tolerated and the procedure produced no overt complications.” (p. 123) Svetlecic et al., Lung 2004;182:119-134.