Neurotoxicity Research

, Volume 11, Issue 2, pp 131–144 | Cite as

Amphetamine and mCPP Effects on Dopamine and Serotonin Striatalin vivo Microdialysates in an Animal Model of Hyperactivity

  • Przemyslaw Nowak
  • Aleksandra Bortel
  • Joanna Dabrowska
  • Joanna Oswiecimska
  • Marzena Drosik
  • Adam Kwiecinski
  • Józef Opara
  • Richard M. Kostrzewa
  • Ryszard Brus


In the neonatally 6-hydroxydopamine (6-OHDA)-lesioned rat hyperlocomotor activity, first described in the 1970s, was subsequently found to be increased by an additional lesion with 5,7-dihydroxytryptamine (5,7-DHT) (i.c.v.) in adulthood. The latter animal model(i.e., 134 μg 6-OHDA at 3 d postbirth plus 75 μg 5,7-DHT at 10 weeks; desipramine pretreatments) was used in this study, in an attempt to attribute hyperlocomotor attenuation by D,L-amphet-amine sulfate (AMPH) and m-chlorophenylpi-perazine di HCl (mCPP), to specific changes in extraneuronal(i.e., in vivo microdialysate) levels of dopamine (DA) and/or serotonin (5-HT). Despite the 98-99% reduction in striatal tissue content of DA, the baseline striatal microdialysate level of DA was reduced by 50% or less at 14 weeks, versus the intact control group. When challenged with AMPH (0.5 mg/kg), the microdialysate level of DA went either unchanged or was slightly reduced over the next 180 min(i.e., 20 min sampling), while in the vehicle group and 5,7-DHT (alone) lesioned group, the microdialysate level was maximally elevated by ~225% and ~450%, respectively - and over a span of nearly 2 h. Acute challenge with mCPP (1 mg/kg salt form) had little effect on microdialysate levels of DA, DOPAC and 5-HT. Moreover, there was no consistent change in the microdialysate levels of DA, DOPAC, and 5-HT between intact, 5-HT-lesioned rats, and DA-lesioned rats which might reasonably account for an attenuation of hyperlocomotor activity. These findings indicate that there are other important neurochemical changes produced by AMPH-and mCPP-attenuated hyperlocomotor activity, or perhaps a different brain region or multiple brain regional effects are involved in AMPH and mCPP behavioral actions.


Biogenic amines 6-Hydroxydopamine 5,7-Dihydroxytryptamine Brain microdialysis ADHD m-Chlorophenylpiperazine Amphetamine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alex KD, GJ Yavanian, HG McFarlane, CP Pluto and EA Pehek (2005) Modulation of dopamine release by striatal 5-HT2C receptors.Synapse 55, 242–251.PubMedCrossRefGoogle Scholar
  2. Aspide R, UA Gioroni Carneval, JA Sergeant and AG Sadile (1998) Non-selective attention and nitric oxide in putative animal models of attention-deficit hyperactivity disorder.Behav. Brain Res. 95, 123–133.PubMedCrossRefGoogle Scholar
  3. Bantick RA, MH De Vries and PM Grasby (2005) The effect of a 5-HT1A receptor agonist on striatal dopamine release.Synapse 57, 67–75.PubMedCrossRefGoogle Scholar
  4. Benloucif S, MJ Keegan and MP Galloway (1993) Serotonin-facilitated dopamine releasein vivo: pharmacological characterization.J. Pharmacol. Exp. Ther. 265, 373–377.PubMedGoogle Scholar
  5. Berger TW, S Kaul, EM Stricker and MJ Zigmond (1985) Hyperinnervation of the striatum by dorsal raphe afferents after dopamine-depleting brain lesions in neonatal rats.Brain Res. 336, 354–358.PubMedCrossRefGoogle Scholar
  6. Biederman J and T Spencer (1999) Attention-deficit/hyperac-tivity disorder (ADHD) as a noradrenergic disorder.Biol. Psychiatry 46, 1234–1242.PubMedCrossRefGoogle Scholar
  7. Bjelke B, I Stromberg, WT O’Connor, B Andbjer, LF Agnati and K Fuxe (1994) Evidence for volume transmission in the dopamine denervated neostriatum of the rat after a unilateral nigral 6-OHDA microinjection. Studies with systemic D- amphetamine treatment.Brain Res. 662, 11–24.PubMedCrossRefGoogle Scholar
  8. Blurton PA and MD Wood (1986) Identification of multiple binding sites for [3H]5-hydroxytryptamine in the rat CNS.J. Neurochem. 46, 1392–1398.PubMedCrossRefGoogle Scholar
  9. Boschert U, DA Amara, L Segu and R Hen (1994) The mouse 5-hydroxytryptamine(1B) receptor is localized predominantly on axon terminals.Neuroscience 58, 167–182.PubMedCrossRefGoogle Scholar
  10. Boyce PJ and JM Finlay (2005) Neonatal depletion of cortical dopamine: effects on dopamine turnover and motor behavior in juvenile and adult rats.Brain Res. Dev. Brain Res. 156, 167–175.PubMedCrossRefGoogle Scholar
  11. Brus R, RM Kostrzewa, KW Perryand RW Fuller(1994) Supersensitization of the oral response to SKF 38393 in neonatal 6-OHDA-lesioned rats is eliminated by neonatal 5,7-dihydroxytryptamine treatment.J. Pharmacol. Exp. Ther. 268, 231–237.PubMedGoogle Scholar
  12. BrusR, P Nowak, R Szkilnik, U Mikolajun and RM Kostrzewa (2004) Serotoninergic attenuate hyperlocomotor activity in rats. Potential new therapeutic strategy for hyperactivity.Neurotoxicity Res. 6, 317–326.CrossRefGoogle Scholar
  13. Butcher SP, IS Fairbrother, JS Kelly and GW Arbuthnott (1988) Amphetamine-induced dopamine release in the rat striatum: anin vivo microdialysis study.J. Neurochem. 50, 346–355.PubMedCrossRefGoogle Scholar
  14. Bymaster FP, JS Katner, DL Nelson, SK Hemrick-Luecke, PG Threlkeld, JH Heiligenstein, SM Morin, DR Gehlert and KW Perry (2002) Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyper-activity disorder.Neuropsychopharmacology 27, 699–711.PubMedCrossRefGoogle Scholar
  15. Castaneda R, N Sussman, R Levy and M Trujillo (1999) A treatment algorithm for attention deficit hyperactivity disorder in cocaine-dependent adults: a one-year private practice study with long-acting stimulants, fluoxetine, and bupro-pion.Subst. Abuse 20, 59–71.CrossRefGoogle Scholar
  16. DeDeurwaerdere P and U Spampinato (2001) The nigrostriatal dopamine system: a neglected target for 5-HT2C receptors.Trends Pharmacol. Sci. 22, 502–504.PubMedCrossRefGoogle Scholar
  17. DeDeurwaerdere P, S Navailles, KA Berg, WP Clarke and US pampinato (2004) Constitutive activity of the serotonin(2C) receptor inhibitsin vivo dopamine release in the rat striatum and nucleus accumbens.J. Neurosci. 24, 3235–3241.PubMedCrossRefGoogle Scholar
  18. Dell’Anna ME, J Luthman, E Lindqvist and L Olsen (1993) Development of monoamine systems after neonatal anoxia in rats.Brain Res. Bull. 32, 159–170.PubMedCrossRefGoogle Scholar
  19. Di Giovanni G, P De Deurwaerdere, M Di Mascio, V Di Matteo, E Esposito and U Spampinato (1999) Selective blockade of serotonin-2C/2B receptors enhances mesolimbic and mesostriatal dopaminergic function: a combinedin vivo electrophysiological and microdialysis study.Neuroscience 91, 587–597.PubMedCrossRefGoogle Scholar
  20. Di Giovanni G, V Di Matteo, M Di Mascio and E Esposito (2000) Preferential modulation of mesolimbicvs. nigrostriatal dopaminergic function by serotonin(2C/2B) receptor agonists: a combinedin vivo electrophysiological and microdialysis study.Synapse 35, 53–61.PubMedCrossRefGoogle Scholar
  21. Elia J, BG Borcherding, JL Rapoport and CS Keysor (1991) Methylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders?Psychiatry Res. 36, 141–155.PubMedCrossRefGoogle Scholar
  22. Eriksson E, G Engberg, O Bingand H Nissbrandt (1999) Effects of mCPP on the extracellular concentrations of serotonin and dopamine in rat brain.Neuropsychopharmacology 20, 287–296.PubMedCrossRefGoogle Scholar
  23. Ernst M, LL Liebenauer, D Tebeka, PH Jons, G Eisenhofer, DL Murphyand AJ Zametkin (1997) Selegiline in ADHD adults: plasma monoamines and monoamine metabolites.Neuropsychopharmacology 16, 276–284.PubMedCrossRefGoogle Scholar
  24. Faraone SV, RH Perlis, AE Doyle, JW Smoller, JJ Goralnick, MA Holmgrenand P Sklar (2005) Molecular genetics of attention-deficit/hyperactivity disorder.Biol. Psychiatry 57, 1313–1323.PubMedCrossRefGoogle Scholar
  25. Galloway MP, CS Suchowski, MJ Keegan and S Hjorth (1993) Local infusion of the selective 5HT-1B agonist CP-93,129 facilitates striatal dopamine releasein vivo.Synapse 15, 90–92.PubMedCrossRefGoogle Scholar
  26. Gobert A, JM Rivet, F Lejeune, A Newman-Tancredi, A Adhumeau-Auclair, JP Nicolas, L Cistarelli, C Melon and MJ Millan (2000) Serotonin(2C) receptors tonically suppress the activity of mesocortical dopaminergic and adren-ergic, but not serotonergic, pathways: a combined dialysis and electrophysiological analysis in the rat.Synapse 36, 205–221.PubMedCrossRefGoogle Scholar
  27. Gong L and RM Kostrzewa (1992) Supersensitized oral responses to a serotonin agonist in neonatal 6-OHDA-treated rats.Pharmacol. Biochem. Behav. 41, 621–623.PubMedCrossRefGoogle Scholar
  28. Gong L, RM Kostrzewa, RW Fuller and KW Perry (1992) Supersensitization of the oral response to SKF 38393 in neonatal 6-OHDA-lesioned rats is mediated through a serotonin system.J. Pharmacol. Exp. Ther. 261, 1000–1007.PubMedGoogle Scholar
  29. Gonon F, F Navarre and M Buda (1984)In vivo monitoring of dopamine release in the rat brain with differential normal pulse voltammetry.Anal. Chem. 56, 573–575.PubMedCrossRefGoogle Scholar
  30. Gresch PJ and PD Walker (1999) Synergistic interaction between serotonin-2 receptor and dopamine D1 receptor stimulation on striatal preprotachykinin mRNA expression in the 6-hydroxydopamine lesioned rat.Brain Res. Mol. Brain Res. 70, 125–134.PubMedCrossRefGoogle Scholar
  31. Heffner TG and LS Seiden (1982) Possible involvement of serotonergic neurons in the reduction of locomotor hyperactivity caused by amphetamine in neonatal rats depleted of brain dopamine.Brain Res. 244, 81–90.PubMedCrossRefGoogle Scholar
  32. Hendley ED, DJ Wessel and J Van Houtten(1986) Inbreeding of Wistar-Kyoto rat strain with hyperactivity but without hypertension.Behav. Neurol. Biol. 45, 1–16.CrossRefGoogle Scholar
  33. Herrera-Marschitz M, J Luthman and S Ferre (1994) Unilateral neonatal intracerebroventricular 6-hydroxydopamine administration in rats: II. Effects on extracellular monoamine, acetylcholine and adenosine levels monitored within vivo microdialysis.Psychopharmacology (Berl.) 116, 451–456.CrossRefGoogle Scholar
  34. Hynd GW, KL Horn and RM Marshall (1991) Neurobiological basis of attention deficit hyperactivity disorder (ADHD).School Psychol. Rev. 20, 174–186.Google Scholar
  35. Johnson SW, NB Mercuri and RA North (1992) 5-hydroxytryptamine(1B) receptors block the GABAB syn-aptic potential in rat dopamine neurons.J. Neurosci. 12, 2000–2006.PubMedGoogle Scholar
  36. Jones SR, JD Joseph, LS Barak, MG Caron and RM Wightman (1999) Dopamine neuronal transport kinetics and effects of amphetamine.J. Neurochem. 73, 2406–2414.PubMedCrossRefGoogle Scholar
  37. Kankaanpaa A, E Meririnne, P Lillsunde and T Seppala(1998) The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens.Pharmacol. Biochem. Behav. 59, 1003–1009.PubMedCrossRefGoogle Scholar
  38. Kasperska A, R Brus, A Sokola, RM Kostrzewa and J Shani (1999) Sexual differentiation in the central dopaminergic effect of nitric oxide donors and inhibitor on stereotyped behavior changes induced by amphetamine, but not by apo-morphine.Pharmacol. Rev. Comm. 10, 329–339.Google Scholar
  39. Khoshbouei H, H Wang, JD Lechleiter, JA Javitch and A Galli (2003) Amphetamine-induced dopamine efflux. A voltage-sensitive and intracellular Na+-dependent mechanism. J.Biol. Chem. 278, 12070–12077.PubMedCrossRefGoogle Scholar
  40. Kirby LG, DS Kreiss, A Singhand I Lucki(1995) Effect of destruction of serotonin neurons on basal and fenfluramine-induced serotonin release in striatum.Synapse 20, 99–105.PubMedCrossRefGoogle Scholar
  41. Kostrzewa RMand L Gong(1991) Supersensitized D1 receptors mediate enhanced oral activity after neonatal 6-OHDA.Pharmacol. Biochem. Behav. 39, 677–682.PubMedCrossRefGoogle Scholar
  42. Kostrzewa RM, L Gongand R Brus(1993) Serotonin (5-HT) systems mediate dopamine (DA) receptor supersensitivity.Acta Neurobiol. Exp. (Wars.) 53, 31–41.Google Scholar
  43. Kostrzewa RM, R Brus, JH Kalbfleish, KW Perry and RW Fuller (1994) Proposed animal model of attention deficit hyperactivity disorder.Brain Res. Bull. 34, 161–167.PubMedCrossRefGoogle Scholar
  44. Kostrzewa RM, TA Reader and L Descarries (1998) Serotonin neural adaptations to ontogenetic loss of dopamine neurons in rat brain.J. Neurochem. 70, 889–898.PubMedCrossRefGoogle Scholar
  45. Kostrzewa RM, P Nowak, JP Kostrzewa, RA Kostrzewa and R Brus(2005) Peculiarities of L-DOPA treatment of Parkinson’s disease.Amino Acids 28, 157–164.PubMedCrossRefGoogle Scholar
  46. Lucki I, HR Ward and A Frazer (1989) Effect of1-(@#@ m-chlorophenyl)piperazine and 9-(m-trifluoromethylphenyl) piperazine on locomotor activity.J. Pharmacol. Exp. Ther. 249, 155–164.PubMedGoogle Scholar
  47. Lucot JBand LS Seiden (1982) Effects of neonatal administration of 5,7-dihydroxytryptamine on locomotor activity.Psychopharmacology (Berl.) 77, 114–116.CrossRefGoogle Scholar
  48. Luthman J, A Fredriksson, T Lewander, G Jonsson and T Archer (1989) Effects of d-amphetamine and methyl-pheni-date on hyperactivity produced by neonatal 6-hydroxydopa-mine treatment.Psychopharmacology (Berl.) 99, 550–557.CrossRefGoogle Scholar
  49. Maeda T, K Kannari, T Suda and M Matsunaga (1999) Loss of regulation by presynaptic dopamine D2 receptors of exogenous L-DOPA-derived dopamine release in the dopaminergic denervated striatum.Brain Res. 817, 185–191.PubMedCrossRefGoogle Scholar
  50. Magara F, L Ricceri, DP Wolfer and HP Lipp (2000) The acallosal mouse strain I/LnJ: a putative model of ADHD?Neurosci. Biobehav. Rev. 24, 45–50.PubMedCrossRefGoogle Scholar
  51. Manrique C, L Segu, F Hery, M Hery, M Faudonand AM Francois-Bellan (1993) Increase of central 5-HT1B binding sites following 5,7-dihydroxytryptamine axotomy in the adult rat.Brain Res. 623, 345–348.PubMedCrossRefGoogle Scholar
  52. Maroteaux L, F Saudou, N Amlaiky, U Boschert, JL Plassat and R Hen(1992) Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centers.Proc. Natl. Acad. Sci. USA 89, 3020–3024.PubMedCrossRefGoogle Scholar
  53. Millan MJ, M Brocco, A Gobert, F Joly, K Bervoets, J Rivet, A Newman-Tancredi, V Audinot and S Maurel (1999) Contrasting mechanisms of action and sensitivity to antipsy-chotics of phencyclidine versus amphetamine: importance of nucleus accumbens 5-HT2A sites for PCP-induced locomotion in the rat.Eur. J. Neurosci. 11, 4419–4432.PubMedCrossRefGoogle Scholar
  54. Miller FE, TG Heffner, C Kotake and LS Seiden (1981) Magnitude and duration of hyperactivity following neonatal 6-hydroxydopamine is related to the extent of brain dopamine depletion.Brain Res. 229, 123–132.PubMedCrossRefGoogle Scholar
  55. Moran-Gates T, K Zhang, RJ Baldessarini and FI Tarazi (2005) Atomoxetine blocks motor hyperactivity in neonatal 6-hydroxydopamine-lesioned rats: implications for treatment of attention-deficit hyperactivity disorder.Int. J. Neuropsychopharmacol. 8, 439–444.PubMedCrossRefGoogle Scholar
  56. Ng NK, HS Lee and PT Wong(1999) Regulation of striatal dopamine release through 5-HT1 and 5-HT2 receptors.J. Neurosci. Res. 55, 600–607.PubMedCrossRefGoogle Scholar
  57. Nowak P, RM Kostrzewa, A Kwiecinski, A Bortel, L Labus and R Brus (2005) Neurotoxic action of 6-hydroxydopamine on the nigrostriatal dopaminergic pathway in rats sensitized with D-amphetamine.J. Physiol. Pharmacol. 56, 325–333.PubMedGoogle Scholar
  58. O’Dell SJ, FB Weihmuller and JF Marshall(1993) Methamphetamine-induced dopamine overflow and injury to striatal dopamine terminals: attenuation by dopamine D1 and D2 antagonists.J. Neurochem. 60, 1792–1799.PubMedCrossRefGoogle Scholar
  59. Paxinos G and C Watson (1986)The Rat Brain in Stereotaxic Coordinates, 2nd Ed. (Academic Press:Sydney).Google Scholar
  60. Puumala T, S Ruotsalainen, P Jakala, E Koivisto, P Riekkinen Jr and J Sirvio (1997) Behavioral and pharmacological studies on the validation of a new animal model for attention deficit hyperactivity disorder.Neurobiol. Learn. Mem. 66, 198–211.CrossRefGoogle Scholar
  61. Radja F,G Daval, M Hamonand D Verge(1992)Pharmacological and physicochemical properties of pre-versus postsynaptic 5-HT1A receptor binding sites in the rat brain: a quantitative autoradiographic study.J. Neurochem. 58, 1338–1346.PubMedCrossRefGoogle Scholar
  62. Richard MGand JP Bennett (1994) Regulation by D2 dopamine receptors ofin vivo dopamine synthesis in striata of rats and mice with experimental parkinsonism.Exp. Neurol. 129, 57–63.PubMedCrossRefGoogle Scholar
  63. Russell VA, T Sagvolden and EB Johansen (2005) Animal models of attention-deficit hyperactivity disorder.Behav. Brain Funct. 1, 9.PubMedCrossRefGoogle Scholar
  64. Sagvolden T (2000) Behavioral validation of the spontaneously hypertensive rats (SHR) as an animal model of attention-deficit/hyperactivity disorder (ADHD).Neurosci. Biobehav. Rev. 24,31–39.PubMedCrossRefGoogle Scholar
  65. Sagvolden T, MA Metzger, HK Schiorbeck, AL Rugland, I Spinnaugr and G Sagvolden (1992) The spontaneously hypertensive rat (SHR) as an animal model of childhood hyperactivity (ADHD): changed reactivity to reinforcers and to psychomotor stimulants.Behav. Neurol. Biol. 58, 103–112.CrossRefGoogle Scholar
  66. Sarhan H, I Cloez-Tayarani, O Massot, MP Fillion and G Fillion (1999) 5-HT1B receptors modulate release of [3H]dopamine from rat striatal synaptosomes.Naunyn Schmiedebergs Arch. Pharmacol. 359, 40–47.PubMedCrossRefGoogle Scholar
  67. Shaywitz BA, JH Klopper and JW Gordon (1976a) Paradoxical response to amphetamine in developing rats treated with 6-hydroxydopamine.Nature 261, 153–155.PubMedCrossRefGoogle Scholar
  68. Shaywitz BA, RD Yagerand JH Klopper(1976b) Selective brain dopamine depletion in developing rats: an experimental model of minimal brain dysfunction.Science 191, 305–308.PubMedCrossRefGoogle Scholar
  69. Silbergeld EKand AM Goldberg(1974) Lead-induced behavioral dysfunction: an animal model of hyperactivity.Exp. Neurol. 42, 146–157.PubMedCrossRefGoogle Scholar
  70. Snyder AM, MJ Zigmond and RD Lund (1986) Sprouting of serotonergic afferents into striatum after dopamine depleting lesions in infant rats: a retrograde transport and immunocy-tochemical study.J. Comp. Neurol. 245, 274–281.PubMedCrossRefGoogle Scholar
  71. Starr HL and J Kemner (2005) Multicenter, randomized, open-label study of OROS methylphenidate versus atomoxetine: treatment outcomes in African-American children with ADHD.J. Natl. Med. Assoc. 97, 11S-16S.PubMedGoogle Scholar
  72. Swanson JM, JA Sergeant, E Taylor, EJS Sonuga-Barke, PS Jansen and DP Canwell (1998) Attention deficit hyperactivity disorder and hyperkinetic disorder.Lancet 351, 429–433.PubMedCrossRefGoogle Scholar
  73. Tseng KY, L Kargieman, S Gacio, LA Riquelme and MG Murer(2005) Consequences of partial and severe dopami-nergic lesion on basal ganglia oscillatory activity and akine-sia.Eur. J. Neurosci. 22, 2579–2586.PubMedCrossRefGoogle Scholar
  74. Wagner J, P Vitali, MG Polfregman, M Zraika and S Hnot (1982) Simultaneous determination of 3,4-dihydroxyphenylalanine, 5-hydroxytryptophan, dopamine, 4-hydroxy-3-methoxyphe-nylalanine, norepinephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, serotonin and 5-hydroxyindolacetic acid in rat cerebrospinal fluid and brain by high-performance liquid chromatography with electrochemical detection.J. Neurochem. 38, 1241–1254.PubMedCrossRefGoogle Scholar
  75. Weiss G(1985) Hyperactivity. Overview and new directions.Psychiatr. Clin. N. Am. 8, 737–753.Google Scholar
  76. Westerink BH(1995) Brain microdialysis and its application for the study of animal behaviour.Behav. Brain Res. 70, 103–124.PubMedCrossRefGoogle Scholar
  77. Zetterström T, T Sharp, CA Marsden and U Ungerstedt (1983)In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after d-amphetamine.J. Neurochem. 41, 1769–1773.PubMedCrossRefGoogle Scholar
  78. Zhang K, E Davids, FI Tarazi and RJ Baldessarini (2002) Effects of dopamine D4 receptor-selective antagonists on motor hyperactivity in rats with neonatal 6-hydroxydopa-mine lesions.Psychopharmacology (Berl.) 161, 100–106.CrossRefGoogle Scholar
  79. Zimmer L, L Rbah, F Giacomelli, D Le Bars and B Renaud (2003) A reduced extracellular serotonin level increases the 5-HT1A PET ligand18F-MPPF binding in the rat hippocampus.J. Nucl. Med. 44, 1495–501.PubMedGoogle Scholar

Copyright information

© FP Graham Publishing Co 2007

Authors and Affiliations

  • Przemyslaw Nowak
    • 1
  • Aleksandra Bortel
    • 1
  • Joanna Dabrowska
    • 1
  • Joanna Oswiecimska
    • 1
  • Marzena Drosik
    • 1
  • Adam Kwiecinski
    • 1
  • Józef Opara
    • 1
  • Richard M. Kostrzewa
    • 2
  • Ryszard Brus
    • 1
  1. 1.Department of PharmacologyMedical University of SilesiaPoland
  2. 2.Department of Pharmacology, Quillen College of MedicineEast Tennessee State UniversityJohnson CityUSA

Personalised recommendations