F. V. Abbott and R. M. Palmour, Morphine-6-glucuronide: Analgesic effects and receptor binding profile in rats, Life Sciences, vol.43, issue.21, pp.1685-1695, 1988.
DOI : 10.1016/0024-3205(88)90479-1

M. Barjavel, P. Sandouk, M. Plotkine, and J. M. Scherrmann, Morphine and morphine metabolite kinetics in the rat brain as assessed by transcortical microdialysis, Life Sciences, vol.55, issue.16, pp.1301-1308, 1994.
DOI : 10.1016/0024-3205(94)90069-8

F. Bourasset, S. Cisternino, J. Temsamani, and J. M. Scherrmann, Evidence for an active transport of morphine-6-??-d-glucuronide but not P-glycoprotein-mediated at the blood-brain barrier, Journal of Neurochemistry, vol.22, issue.6, pp.1564-1567, 2003.
DOI : 10.1046/j.1471-4159.2003.01990.x

F. Bourasset, K. Bernard, C. Munoz, P. Genissel, and J. M. Scherrmann, Neuropharmacokinetics of a new alpha-amino-3-hydroxy-5-methyl-4-iso- xazole propionic acid (AMPA) modulator, Drug Metabolism and Disposition, vol.23412, issue.338, pp.189864-189865, 2005.

P. M. Bungay, P. F. Morrison, and R. L. Dedrick, Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vitro, Life Sciences, vol.46, issue.2, pp.105-119, 1990.
DOI : 10.1016/0024-3205(90)90043-Q

A. E. Busch, U. Karbach, D. Miska, V. Gorboulev, A. Akhoundova et al., Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters , amantadine, and memantine, Molecular Pharmacology, vol.54, issue.2, pp.342-352, 1998.

C. B. Christensen and L. N. Jorgensen, Morphine-6-glucuronide Has High Affinity for the Opioid Receptor, Pharmacology & Toxicology, vol.16, issue.1, pp.75-76, 1987.
DOI : 10.1111/j.1600-0773.1987.tb01724.x

S. Cisternino, C. Rousselle, C. Dagenais, and J. M. Scherrmann, Screening of multidrug-resistance sensitive drugs by in situ brain perfusion in P-glycoprotein-deficient mice, Pharmaceutical Research, vol.18, issue.2, pp.183-190, 2001.
DOI : 10.1023/A:1011080418027

S. Dallas, X. Zhu, S. Baruchel, L. Schlichter, and R. Bendayan, Functional Expression of the Multidrug Resistance Protein 1 in Microglia, Journal of Pharmacology and Experimental Therapeutics, vol.307, issue.1, pp.282-290, 2003.
DOI : 10.1124/jpet.103.054304

S. Dallas, L. Schlichter, and R. Bendayan, MRP4- and MRP5-mediated efflux of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) by microglia, Clinical Pharmacology & Therapeutics, vol.75, issue.2, pp.1221-1229, 2004.
DOI : 10.1016/j.clpt.2003.11.241

X. Decleves, A. Regina, J. L. Laplanche, F. Roux, B. Boval et al., Functional expression of p-glycoprotein and multidrug resistance-associated protein (mrp1) in primary cultures of rat astrocytes, Journal of Neuroscience Research, vol.273, issue.5, pp.594-601, 2000.
DOI : 10.1002/(SICI)1097-4547(20000601)60:5<594::AID-JNR4>3.0.CO;2-6

Y. Deguchi, K. Inabe, K. Tomiyasu, K. Nozawa, S. Yamada et al., Study on brain interstitial fluid distribution and blood ? brain barrier transport of baclofen in rats by microdialysis [published erratum appears in, Pharm Res Pharmaceutical Research, vol.13, issue.1212, pp.647-1838, 1995.

B. Frances, R. Gout, B. Monsarrat, J. Cros, and J. M. Zajac, Further evidence that morphine-6 beta-glucuronide is a more potent opioid agonist than morphine, Journal of Pharmacology and Experimental Therapeutics, vol.262, issue.1, pp.25-31, 1992.

D. Grundemann, V. Gorboulev, S. Gambaryan, M. Veyhl, and H. Koepsell, Drug excretion mediated by a new prototype of polyspecific transporter, Nature, vol.74, issue.6506, pp.549-552, 1994.
DOI : 10.1006/abio.1987.9999

M. H. Hanna, K. M. Elliott, and M. Fung, Randomized, Double-blind Study of the Analgesic Efficacy of Morphine-6-Glucuronide versus Morphine Sulfate for Postoperative Pain in Major Surgery, Anesthesiology, vol.102, issue.4, pp.815-821, 2005.
DOI : 10.1097/00000542-200504000-00018

A. Kakee, H. Takanaga, T. Terasaki, M. Naito, T. Tsuruo et al., Efflux of a suppressive neurotransmitter, GABA, across the blood-brain barrier, Journal of Neurochemistry, vol.20, issue.1, pp.110-118, 2001.
DOI : 10.1046/j.1471-4159.2001.00540.x

G. J. Kilpatrick and T. W. Smith, Morphine-6-glucuronide: Actions and mechanisms, Medicinal Research Reviews, vol.270, issue.5, pp.521-544, 2005.
DOI : 10.1002/med.20035

G. Lee, S. Dallas, M. Hong, and R. Bendayan, Drug transporters in the central nervous system: brain barriers and brain parenchyma considerations, Pharmacological Reviews, vol.53, issue.4, pp.569-596, 2001.

G. Lee, L. Schlichter, M. Bendayan, and R. Bendayan, Functional expression of P-glycoprotein in rat brain microglia, Journal of Pharmacology and Experimental Therapeutics, vol.299, issue.1, pp.204-212, 2001.

J. Lö-tsch, R. Schmidt, G. Vetter, H. Schmidt, C. Skarke et al., The influence of inhibition of probenecid sensitive transporters on the central nervous system (CNS) uptake and the antinociceptive activity of morphine-6-glucuronide in rats, Neuroscience Letters, vol.329, issue.2, p.145, 2002.
DOI : 10.1016/S0304-3940(02)00618-3

M. Doan, K. M. Boje, and K. M. , Theoretical pharmacokinetic and pharmacodynamic simulations of drug delivery mediated by blood-brain barrier transporters, Biopharmaceutics & Drug Disposition, vol.91, issue.7, pp.261-278, 2000.
DOI : 10.1002/bdd.242

C. Mercier, X. Decleves, C. Masseguin, P. Fragner, M. Tardy et al., P-glycoprotein (ABCB1) but not multidrug resistance-associated protein 1 (ABCC1) is induced by doxorubicin in primary cultures of rat astrocytes, Journal of Neurochemistry, vol.20, issue.4, pp.820-830, 2003.
DOI : 10.1046/j.1471-4159.2003.02034.x

C. Mercier, C. Masseguin, F. Roux, J. Gabrion, and J. M. Scherrmann, Expression of P-glycoprotein (ABCB1) and Mrp1 (ABCC1) in adult rat brain: focus on astrocytes, Brain Research, vol.1021, issue.1, pp.32-40, 2004.
DOI : 10.1016/j.brainres.2004.06.034

L. J. Murphey and G. D. Olsen, Diffusion of morphine-6-beta-d-glucuronide into the neonatal guinea pig brain during drug-induced respiratory depression, Journal of Pharmacology and Experimental Therapeutics, vol.271, issue.1, pp.118-124, 1994.

T. Okura, M. Saito, M. Nakanishi, N. Komiyama, A. Fujii et al., -glucuronide after intracerebroventricular injection in rats, British Journal of Pharmacology, vol.16, issue.1, pp.211-217, 2003.
DOI : 10.1038/sj.bjp.0705418

URL : https://hal.archives-ouvertes.fr/hal-00752093

P. B. Osborne, B. Chieng, and M. J. Christie, -glucuronide has a higher efficacy than morphine as a mu-opioid receptor agonist in the rat locus coeruleus, British Journal of Pharmacology, vol.22, issue.7, pp.1422-1428, 2000.
DOI : 10.1038/sj.bjp.0703697

URL : https://hal.archives-ouvertes.fr/in2p3-00956389

G. W. Pasternak, R. J. Bodnar, J. A. Clark, and C. E. Inturrisi, Morphine-6-glucuronide, a potent mu agonist, Life Sciences, vol.41, issue.26, pp.2845-2849, 1987.
DOI : 10.1016/0024-3205(87)90431-0

D. Paul, K. M. Standifer, C. E. Inturrisi, and G. W. Pasternak, Pharmacological characterization of morphine-6 beta-glucuronide, a very potent morphine metabolite, Journal of Pharmacology and Experimental Therapeutics, vol.251, issue.2, pp.477-483, 1989.

G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates, 1998.

R. Romberg, E. Olofsen, E. Sarton, L. Teppema, and A. Dahan, Pharmacodynamic Effect of Morphine-6-glucuronide versus Morphine on Hypoxic and Hypercapnic Breathing in Healthy Volunteers, Anesthesiology, vol.99, issue.4, pp.788-798, 2003.
DOI : 10.1097/00000542-200310000-00008

G. Schill and K. Gustavii, Acid Dissociation Constants of Morphine, Acta Pharmaceutica Suecica, vol.19, pp.24-35, 1964.

J. L. Scism, K. M. Powers, A. A. Artru, A. C. Chambers, L. Lewis et al., Effects of probenecid on brain ? cerebrospinal fluid ? blood distribution kinetics of E-Delta 2-valproic acid in rabbits, Drug Metabolism and Disposition, vol.25, issue.12, pp.1337-1346, 1997.

K. Shimomura, O. Kamata, S. Ueki, S. Ida, and K. Oguri, Analgesic Effect of Morphine Glucuronides, The Tohoku Journal of Experimental Medicine, vol.105, issue.1, pp.45-52, 1971.
DOI : 10.1620/tjem.105.45

C. Skarke, M. Langer, M. Jarrar, H. Schmidt, G. Geisslinger et al., Probenecid Interacts with the Pharmacokinetics of Morphine-6-glucuronide in Humans, Anesthesiology, vol.101, issue.6, pp.1394-1399, 2004.
DOI : 10.1097/00000542-200412000-00020

F. Stain, M. J. Barjavel, P. Sandouk, M. Plotkine, J. M. Scherrmann et al., Analgesic response and plasma and brain extracellular fluid pharmacokinetics of morphine and morphine-6-beta-d-glucuro- nide in the rat, Journal of Pharmacology and Experimental Therapeutics, vol.274, issue.2, pp.852-857, 1995.

F. Stain-texier, G. Boschi, P. Sandouk, and J. M. Scherrmann, Elevated concentrations of morphine 6-beta-D-glucuronide in brain extracellular fluid despite low blood-brain barrier permeability, British Journal of Pharmacology, vol.22, issue.4, pp.917-924, 1999.
DOI : 10.1038/sj.bjp.0702873

D. Sugiyama, H. Kusuhara, Y. Shitara, T. Abe, P. J. Meier et al., Characterization of the efflux transport of 17beta-estradiol-d-17beta-glucuronide from the brain across the blood ? brain barrier, Journal of Pharmacology and Experimental Therapeutics, vol.298, issue.1, pp.316-322, 2001.

H. Sun, P. M. Bungay, and W. F. Elmquist, Effect of capillary efflux transport inhibition on the determination of probe recovery during in vivo microdialysis in the brain, Journal of Pharmacology and Experimental Therapeutics, vol.297, issue.3, pp.991-1000, 2001.

D. H. Sweet and J. B. Pritchard, rOCT2 is a basolateral potential-driven carrier, not an organic cation/proton exchanger, American Journal of Physiology, vol.2776, issue.2, pp.890-898, 1999.

K. Tunblad, E. N. Jonsson, and M. Hammarlund-udenaes, Morphine blood ? brain barrier transport is influenced by probenecid co-administration, Pharmaceutical Research, vol.20, issue.4, pp.618-623, 2003.
DOI : 10.1023/A:1023250900462

K. Tunblad, M. Hammarlund-udenaes, and E. N. Jonsson, Influence of probenecid on the delivery of morphine-6-glucuronide to the brain, European Journal of Pharmaceutical Sciences, vol.24, issue.1, pp.49-57, 2005.
DOI : 10.1016/j.ejps.2004.09.009

X. Wu, R. Kekuda, W. Huang, Y. J. Fei, F. H. Leibach et al., Identity of the Organic Cation Transporter OCT3 as the Extraneuronal Monoamine Transporter (uptake2) and Evidence for the Expression of the Transporter in the Brain, Journal of Biological Chemistry, vol.273, issue.49, pp.32776-32786, 1998.
DOI : 10.1074/jbc.273.49.32776

R. Xie, M. Hammarlund-udenaes, A. G. De-boer, and E. C. De-lange, (+/+) mice, British Journal of Pharmacology, vol.15, issue.3, pp.563-568, 1999.
DOI : 10.1038/sj.bjp.0702804

N. Zelcer, K. Van-de-wetering, M. Hillebrand, E. Sarton, A. Kuil et al., Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception, Proceedings of the National Academy of Sciences of the United States of America, pp.7274-7279, 2005.
DOI : 10.1073/pnas.0502530102