Skip to main content
Erschienen in: Forensic Toxicology 1/2017

19.08.2016 | Original Article

Changes in dopamine, serotonin and their metabolites in brain microdialysates from rats following exposure to new psychoactive drugs

verfasst von: Minjeong Kim, Da Hye Kim, Yong Sup Lee, Choon-Gon Jang, Chae Ha Yang, Sooyeun Lee

Erschienen in: Forensic Toxicology | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

New psychoactive drugs (NPDs), or so-called “designer drugs” are chemically transformed compounds of traditional drugs of abuse for the purpose of evading crackdown. The abuse of NPDs is a significant social problem and threatens public health; however, few studies on their effects on the central nervous system have been conducted. Microdialysis is a useful in vivo sampling technique in neurochemistry because it enables monitoring of synaptic release of neurotransmitters by drug exposure or other stimuli in real time. Dopamine (DA) and serotonin (5-HT) are important neurotransmitters associated with drug abuse and addiction. In this study, changes of DA, 5-HT and their metabolites in brain microdialysates from rats following exposure to selected 11 NPDs (MPA, 5-APDB, PCA, α-PVT, AB-PINACA, QUPIC, 5-fluoropentyl-3-pyridinoylindole, AMT, NMT, 4-OH-DET and desoxy-D2PM, 0.3, 1 and 3 mg/kg, consecutively, intraperitoneally) were investigated using a validated liquid chromatography –tandem mass spectrometry method. Most NPDs affected the extracellular levels of DA, 5-HT and/or their metabolites, showing consistent changes depending on the groups of chemical structures, such as amphetamines, synthetic cannabinoids and tryptamines. Significant DA and/or 5-HT increases were observed for all the amphetamine analogues. Weak fluctuations of DA and/or 5-HT concentrations were observed following exposure to synthetic cannabinoids and more severe fluctuations were shown by the tryptamines. The current results could be used as the preliminary data for further research concerning monoamine neurotransmitter-related mechanisms of NPDs. Moreover, the understanding gained from this research could be helpful to monitor the liability of NPD abuse and addiction.
Literatur
1.
Zurück zum Zitat Liechti M (2015) Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signaling. Swiss Med Wkly 145:w14043PubMed Liechti M (2015) Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signaling. Swiss Med Wkly 145:w14043PubMed
2.
Zurück zum Zitat Zawilska JB, Andrzejczak D (2015) Next generation of novel psychoactive substances on the Horizon–a complex problem to face. Drug Alcohol Depend 157:1–17CrossRefPubMed Zawilska JB, Andrzejczak D (2015) Next generation of novel psychoactive substances on the Horizon–a complex problem to face. Drug Alcohol Depend 157:1–17CrossRefPubMed
3.
Zurück zum Zitat Anderzhanova E, Wotjak CT (2013) Brain microdialysis and its applications in experimental neurochemistry. Cell Tissue Res 354:27–39CrossRefPubMed Anderzhanova E, Wotjak CT (2013) Brain microdialysis and its applications in experimental neurochemistry. Cell Tissue Res 354:27–39CrossRefPubMed
4.
Zurück zum Zitat Boschi G, Scherrmann J (2000) Microdialysis in mice for drug delivery research. Adv Drug Deliv Rev 45:271–281CrossRefPubMed Boschi G, Scherrmann J (2000) Microdialysis in mice for drug delivery research. Adv Drug Deliv Rev 45:271–281CrossRefPubMed
5.
Zurück zum Zitat Plock N, Kloft C (2005) Microdialysis—theoretical background and recent implementation in applied life-sciences. Eur J Pharm Sci 25:1–24CrossRefPubMed Plock N, Kloft C (2005) Microdialysis—theoretical background and recent implementation in applied life-sciences. Eur J Pharm Sci 25:1–24CrossRefPubMed
6.
Zurück zum Zitat Darvesh AS, Carroll RT, Geldenhuys WJ, Gudelsky GA, Klein J, Meshul CK, Van der Schyf CJ (2011) In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery. Expert Opin Drug Discov 6:109–127CrossRefPubMedPubMedCentral Darvesh AS, Carroll RT, Geldenhuys WJ, Gudelsky GA, Klein J, Meshul CK, Van der Schyf CJ (2011) In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery. Expert Opin Drug Discov 6:109–127CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Chaurasia CS, Chen CE, Ashby CR Jr (1999) In vivo on-line HPLC-microdialysis: simultaneous detection of monoamines and their metabolites in awake freely-moving rats. J Pharm Biomed Anal 19:413–422CrossRefPubMed Chaurasia CS, Chen CE, Ashby CR Jr (1999) In vivo on-line HPLC-microdialysis: simultaneous detection of monoamines and their metabolites in awake freely-moving rats. J Pharm Biomed Anal 19:413–422CrossRefPubMed
8.
Zurück zum Zitat Nirogi R, Komarneni P, Kandikere V, Boggavarapu R, Bhyrapuneni G, Benade V, Gorentla S (2013) A sensitive and selective quantification of catecholamine neurotransmitters in rat microdialysates by pre-column dansyl chloride derivatization using liquid chromatography-tandem mass spectrometry. J Chromatogr B 913-914:41–47CrossRef Nirogi R, Komarneni P, Kandikere V, Boggavarapu R, Bhyrapuneni G, Benade V, Gorentla S (2013) A sensitive and selective quantification of catecholamine neurotransmitters in rat microdialysates by pre-column dansyl chloride derivatization using liquid chromatography-tandem mass spectrometry. J Chromatogr B 913-914:41–47CrossRef
9.
Zurück zum Zitat Greco S, Danysz W, Zivkovic A, Gross R, Stark H (2013) Microdialysate analysis of monoamine neurotransmitters—a versatile and sensitive LC–MS/MS method. Anal Chim Acta 771:65–72CrossRefPubMed Greco S, Danysz W, Zivkovic A, Gross R, Stark H (2013) Microdialysate analysis of monoamine neurotransmitters—a versatile and sensitive LC–MS/MS method. Anal Chim Acta 771:65–72CrossRefPubMed
10.
Zurück zum Zitat Cannazza G, Carrozzo MM, Cazzato AS, Bretis IM, Troisi L, Parenti C, Braghiroli D, Guiducci S, Zoli M (2012) Simultaneous measurement of adenosine, dopamine, acetylcholine and 5-hydroxytryptamine in cerebral mice microdialysis samples by LC–ESI-MS/MS. J Pharm Biomed Anal 71:183–186CrossRefPubMed Cannazza G, Carrozzo MM, Cazzato AS, Bretis IM, Troisi L, Parenti C, Braghiroli D, Guiducci S, Zoli M (2012) Simultaneous measurement of adenosine, dopamine, acetylcholine and 5-hydroxytryptamine in cerebral mice microdialysis samples by LC–ESI-MS/MS. J Pharm Biomed Anal 71:183–186CrossRefPubMed
11.
Zurück zum Zitat Parrot S, Neuzeret PC, Denoroy L (2011) A rapid and sensitive method for the analysis of brain monoamine neurotransmitters using ultra-fast liquid chromatography coupled to electrochemical detection. J Chromatogr B 879:3871–3878CrossRef Parrot S, Neuzeret PC, Denoroy L (2011) A rapid and sensitive method for the analysis of brain monoamine neurotransmitters using ultra-fast liquid chromatography coupled to electrochemical detection. J Chromatogr B 879:3871–3878CrossRef
12.
Zurück zum Zitat Yoshitake T, Kehr J, Yoshitake S, Fujino K, Nohta H, Yamaguchi M (2004) Determination of serotonin, noradrenaline, dopamine and their metabolites in rat brain extracts and microdialysis samples by column liquid chromatography with fluorescence detection following derivatization with benzylamine and 1,2-diphenylethylenediamine. J Chromatogr B 807:177–183CrossRef Yoshitake T, Kehr J, Yoshitake S, Fujino K, Nohta H, Yamaguchi M (2004) Determination of serotonin, noradrenaline, dopamine and their metabolites in rat brain extracts and microdialysis samples by column liquid chromatography with fluorescence detection following derivatization with benzylamine and 1,2-diphenylethylenediamine. J Chromatogr B 807:177–183CrossRef
13.
Zurück zum Zitat Gingrich JA, Hen R (2001) Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout mice. Psychopharmacology 155:1–10CrossRefPubMed Gingrich JA, Hen R (2001) Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout mice. Psychopharmacology 155:1–10CrossRefPubMed
14.
Zurück zum Zitat Hirao K, Pontone GM, Smith GS (2015) Molecular imaging of neuropsychiatric symptoms in Alzheimer’s and Parkinson’s disease. Neurosci Biobehav Rev 49:157–170CrossRefPubMed Hirao K, Pontone GM, Smith GS (2015) Molecular imaging of neuropsychiatric symptoms in Alzheimer’s and Parkinson’s disease. Neurosci Biobehav Rev 49:157–170CrossRefPubMed
15.
Zurück zum Zitat Iversen L, White M, Treble R (2014) Designer psychostimulants: pharmacology and differences. Neuropharmacology 87:59–65CrossRefPubMed Iversen L, White M, Treble R (2014) Designer psychostimulants: pharmacology and differences. Neuropharmacology 87:59–65CrossRefPubMed
16.
Zurück zum Zitat Matsumoto T, Maeno Y, Kato H, Seko-Nakamura Y, Monma-Ohtaki J, Ishiba A, Nagao M, Aoki Y (2014) 5-Hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis. Eur Neuropsychopharmacol 24:1362–1370CrossRefPubMed Matsumoto T, Maeno Y, Kato H, Seko-Nakamura Y, Monma-Ohtaki J, Ishiba A, Nagao M, Aoki Y (2014) 5-Hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis. Eur Neuropsychopharmacol 24:1362–1370CrossRefPubMed
17.
Zurück zum Zitat Kehr J, Ichinose F, Yoshitake S, Goiny M, Sievertsson T, Nyberg F, Yoshitake T (2011) Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. Br J Pharmacol 164:1949–1958CrossRefPubMedPubMedCentral Kehr J, Ichinose F, Yoshitake S, Goiny M, Sievertsson T, Nyberg F, Yoshitake T (2011) Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. Br J Pharmacol 164:1949–1958CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Kim M, Lee JG, Yang CH, Lee S (2016) Silica stationary phase-based on-line sample enrichment coupled with LC–MS/MS for the quantification of dopamine, serotonin and their metabolites in rat brain microdialysates. Anal Chim Acta 923:55–65CrossRefPubMed Kim M, Lee JG, Yang CH, Lee S (2016) Silica stationary phase-based on-line sample enrichment coupled with LC–MS/MS for the quantification of dopamine, serotonin and their metabolites in rat brain microdialysates. Anal Chim Acta 923:55–65CrossRefPubMed
19.
Zurück zum Zitat Zhao RJ, Yoon SS, Lee BH, Kwon YK, Kim KJ, Shim I, Choi KH, Kim MR, Golden GT, Yang CH (2006) Acupuncture normalizes the release of accumbal dopamine during the withdrawal period and after the ethanol challenge in chronic ethanol-treated rats. Neurosci Lett 395:28–32CrossRefPubMed Zhao RJ, Yoon SS, Lee BH, Kwon YK, Kim KJ, Shim I, Choi KH, Kim MR, Golden GT, Yang CH (2006) Acupuncture normalizes the release of accumbal dopamine during the withdrawal period and after the ethanol challenge in chronic ethanol-treated rats. Neurosci Lett 395:28–32CrossRefPubMed
20.
Zurück zum Zitat Zaitsu K, Hayashi Y, Kusano M, Tsuchihashi H, Ishii A (2016) Application of metabolomics to toxicology of drugs of abuse: a mini review of metabolomics approach to acute and chronic toxicity studies. Drug Metab Pharmacokinet 31:21–26CrossRefPubMed Zaitsu K, Hayashi Y, Kusano M, Tsuchihashi H, Ishii A (2016) Application of metabolomics to toxicology of drugs of abuse: a mini review of metabolomics approach to acute and chronic toxicity studies. Drug Metab Pharmacokinet 31:21–26CrossRefPubMed
21.
Zurück zum Zitat Welter-Luedeke J, Maurer HH (2016) New psychoactive substances: chemistry, pharmacology, metabolism, and detectability of amphetamine derivatives with modified ring systems. Ther Drug Monit 38:4–11CrossRefPubMed Welter-Luedeke J, Maurer HH (2016) New psychoactive substances: chemistry, pharmacology, metabolism, and detectability of amphetamine derivatives with modified ring systems. Ther Drug Monit 38:4–11CrossRefPubMed
22.
Zurück zum Zitat Kaizaki A, Tanaka S, Numazawa S (2014) New recreational drug 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (alpha-PVP) activates central nervous system via dopaminergic neuron. J Toxicol Sci 39:1–6CrossRefPubMed Kaizaki A, Tanaka S, Numazawa S (2014) New recreational drug 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (alpha-PVP) activates central nervous system via dopaminergic neuron. J Toxicol Sci 39:1–6CrossRefPubMed
23.
Zurück zum Zitat Marusich JA, Antonazzo KR, Wiley JL, Blough BE, Partilla JS, Baumann MH (2014) Pharmacology of novel synthetic stimulants structurally related to the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology 87:206–213CrossRefPubMedPubMedCentral Marusich JA, Antonazzo KR, Wiley JL, Blough BE, Partilla JS, Baumann MH (2014) Pharmacology of novel synthetic stimulants structurally related to the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology 87:206–213CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Kolanos R, Sakloth F, Jain AD, Partilla JS, Baumann MH, Glennon RA (2015) Structural modification of the designer stimulant α-pyrrolidinovalerophenone (α-PVP) influences potency at dopamine transporters. ACS Chem Neurosci 6:1726–1731CrossRefPubMed Kolanos R, Sakloth F, Jain AD, Partilla JS, Baumann MH, Glennon RA (2015) Structural modification of the designer stimulant α-pyrrolidinovalerophenone (α-PVP) influences potency at dopamine transporters. ACS Chem Neurosci 6:1726–1731CrossRefPubMed
25.
Zurück zum Zitat Monte AP, Marona-Lewicka D, Cozzi NV, Nichols DE (1993) Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogues of 3,4-(methylenedioxy)amphetamine. J Med Chem 36:3700–3706CrossRefPubMed Monte AP, Marona-Lewicka D, Cozzi NV, Nichols DE (1993) Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogues of 3,4-(methylenedioxy)amphetamine. J Med Chem 36:3700–3706CrossRefPubMed
26.
27.
Zurück zum Zitat Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL (2013) Neurochemical profiles of some novel psychoactive substances. Eur J Pharmacol 700:147–151CrossRefPubMed Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL (2013) Neurochemical profiles of some novel psychoactive substances. Eur J Pharmacol 700:147–151CrossRefPubMed
28.
Zurück zum Zitat Johnson MP, Huang XM, Oberlender R, Nash JF, Nichols DE (1990) Behavioral, biochemical and neurotoxicological actions of the α-ethyl homologue of p-chloroamphetamine. Eur J Pharmacol 191:1–10CrossRefPubMed Johnson MP, Huang XM, Oberlender R, Nash JF, Nichols DE (1990) Behavioral, biochemical and neurotoxicological actions of the α-ethyl homologue of p-chloroamphetamine. Eur J Pharmacol 191:1–10CrossRefPubMed
29.
Zurück zum Zitat Lanteri C, Salomon L, Torrens Y, Glowinski J, Tassin JP (2008) Drugs of abuse specifically sensitize noradrenergic and serotonergic neurons via a non-dopaminergic mechanism. Neuropsychopharmacology 33:1724–1734CrossRefPubMed Lanteri C, Salomon L, Torrens Y, Glowinski J, Tassin JP (2008) Drugs of abuse specifically sensitize noradrenergic and serotonergic neurons via a non-dopaminergic mechanism. Neuropsychopharmacology 33:1724–1734CrossRefPubMed
30.
Zurück zum Zitat Saadat KS, Elliott JM, Colado MI, Green AR (2006) The acute and long-term neurotoxic effects of MDMA on marble burying behaviour in mice. J Psychopharmacol 20:264–271CrossRefPubMed Saadat KS, Elliott JM, Colado MI, Green AR (2006) The acute and long-term neurotoxic effects of MDMA on marble burying behaviour in mice. J Psychopharmacol 20:264–271CrossRefPubMed
31.
Zurück zum Zitat Murnane KS, Perrine SA, Finton BJ, Galloway MP, Howell LL, Fantegrossi WE (2012) Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: correlations between behavior and neurochemistry. Psychopharmacology 220:495–508CrossRefPubMed Murnane KS, Perrine SA, Finton BJ, Galloway MP, Howell LL, Fantegrossi WE (2012) Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: correlations between behavior and neurochemistry. Psychopharmacology 220:495–508CrossRefPubMed
32.
Zurück zum Zitat De Luca MA, Bimpisidis Z, Melis M, Marti M, Caboni P, Valentini V, Margiani G, Pintori N, Polis I, Marsicano G, Parsons LH, Di Chiara G (2015) Stimulation of in vivo dopamine transmission and intravenous self-administration in rats and mice by JWH-018, a Spice cannabinoid. Neuropharmacology 99:705–714CrossRefPubMed De Luca MA, Bimpisidis Z, Melis M, Marti M, Caboni P, Valentini V, Margiani G, Pintori N, Polis I, Marsicano G, Parsons LH, Di Chiara G (2015) Stimulation of in vivo dopamine transmission and intravenous self-administration in rats and mice by JWH-018, a Spice cannabinoid. Neuropharmacology 99:705–714CrossRefPubMed
33.
Zurück zum Zitat Ossato A, Canazza I, Trapella C, Vincenzi F, De Luca MA, Rimondo C, Varani K, Borea PA, Serpelloni G, Marti M (2016) Effect of JWH-250, JWH-073 and their interaction on "tetrad", sensorimotor, neurological and neurochemical responses in mice. Prog Neuropsychopharmacol Biol Psychiatry 67:31–50CrossRefPubMed Ossato A, Canazza I, Trapella C, Vincenzi F, De Luca MA, Rimondo C, Varani K, Borea PA, Serpelloni G, Marti M (2016) Effect of JWH-250, JWH-073 and their interaction on "tetrad", sensorimotor, neurological and neurochemical responses in mice. Prog Neuropsychopharmacol Biol Psychiatry 67:31–50CrossRefPubMed
34.
Zurück zum Zitat De Luca MA, Castelli MP, Loi B, Porcu A, Martorelli M, Miliano C, Kellett K, Davidson C, Stair JL, Schifano F, Di Chiara G (2015) Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135. Neuropharmacology 105:630–638CrossRefPubMed De Luca MA, Castelli MP, Loi B, Porcu A, Martorelli M, Miliano C, Kellett K, Davidson C, Stair JL, Schifano F, Di Chiara G (2015) Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135. Neuropharmacology 105:630–638CrossRefPubMed
35.
Zurück zum Zitat Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (2014) Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes. Psychopharmacology 231:4135–4144CrossRefPubMedPubMedCentral Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (2014) Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes. Psychopharmacology 231:4135–4144CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Nagai F, Nonaka R, Satoh K, Kamimura H (2007) The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. Eur J Pharmacol 559:132–137CrossRefPubMed Nagai F, Nonaka R, Satoh K, Kamimura H (2007) The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. Eur J Pharmacol 559:132–137CrossRefPubMed
37.
Zurück zum Zitat Arunotayanun W, Dalley JW, Huang XP, Setola V, Treble R, Iversen L, Roth BL, Gibbons S (2013) An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging novel psychoactive drugs. Bioorg Med Chem Lett 23:3411–3415CrossRefPubMed Arunotayanun W, Dalley JW, Huang XP, Setola V, Treble R, Iversen L, Roth BL, Gibbons S (2013) An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging novel psychoactive drugs. Bioorg Med Chem Lett 23:3411–3415CrossRefPubMed
38.
Zurück zum Zitat Sakashita Y, Abe K, Katagiri N, Kambe T, Saitoh T, Utsunomiya I, Horiguchi Y, Taguchi K (2015) Effect of psilocin on extracellular dopamine and serotonin levels in the mesoaccumbens and mesocortical pathway in awake rats. Biol Pharm Bull 38:134–138CrossRefPubMed Sakashita Y, Abe K, Katagiri N, Kambe T, Saitoh T, Utsunomiya I, Horiguchi Y, Taguchi K (2015) Effect of psilocin on extracellular dopamine and serotonin levels in the mesoaccumbens and mesocortical pathway in awake rats. Biol Pharm Bull 38:134–138CrossRefPubMed
39.
Zurück zum Zitat Simmler LD, Rickli A, Schramm Y, Hoener MC, Liechti ME (2014) Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives. Biochem Pharmacol 88:237–244CrossRefPubMed Simmler LD, Rickli A, Schramm Y, Hoener MC, Liechti ME (2014) Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives. Biochem Pharmacol 88:237–244CrossRefPubMed
40.
Zurück zum Zitat Davidson C, Ramsey J (2012) Desoxypipradrol is more potent than cocaine on evoked dopamine efflux in the nucleus accumbens. J Psychopharmacol 26:1036–1041CrossRefPubMed Davidson C, Ramsey J (2012) Desoxypipradrol is more potent than cocaine on evoked dopamine efflux in the nucleus accumbens. J Psychopharmacol 26:1036–1041CrossRefPubMed
Metadaten
Titel
Changes in dopamine, serotonin and their metabolites in brain microdialysates from rats following exposure to new psychoactive drugs
verfasst von
Minjeong Kim
Da Hye Kim
Yong Sup Lee
Choon-Gon Jang
Chae Ha Yang
Sooyeun Lee
Publikationsdatum
19.08.2016
Verlag
Springer Japan
Erschienen in
Forensic Toxicology / Ausgabe 1/2017
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-016-0335-8

Weitere Artikel der Ausgabe 1/2017

Forensic Toxicology 1/2017 Zur Ausgabe

Neu im Fachgebiet Rechtsmedizin