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Contents: pp. 6 - 15 Monoamines in the Brain under the Influence of Muscimol and Ibotenic Acid, Two Psychoactive Principles of Amanita Muscaria P. Konig-Persin et al - Psychopharmacologia 1970 pp. 16 - 19 Amanita Muscaria and the Thunderbolt Legend in Guatemala and Mexico B. Lowy - Mycologia 1974 pp. 20 - 24 Russian Use of Amanita Muscaria - A Footnote to Wasson's Soma Ethel Dunn - Current Anthropology 1973 pp. 25 - 28 Traditional Use in North America of Amanita Muscaria R. Gordon Wasson - Journal of Psychedelic Drugs 1979 pp. 30 - 60 Soma and Amanita Muscaria John Brough CTAKL 1981 pp. 61 - 66 Microbore Single-Column Analysis of Pharmacologically Active Alkaloids from the Fly Agaric Mushroom Amanita Muscaria Gore & Jordan - Journal of Chromatography 1982 pp. 67 - 82 2,3 - and 4,5 Secodopa, the Biosynthetic IntermediatesGenerated from L-Dopa by an Enzyme System Extracted from the Amanita Muscaria L, and Their Spontaneous Conversion to Muscaflavin and Betalamic Acid, Respectively, and Betalains Terradas & Wyler Helvetica Chima Acta 1991 pp. 83 - 97 Amanita Muscaria : chemistry, biology, toxicology, and ethnomycology Diderot & Melendez-Howell - British Mycological Society 2003 pp. 98 - 100 Fly Agaric ( Amanita Muscaria)Poisoning: Case Report and Review Satora et al - Toxicon 2005 pp. 101 - 118 Ethnomycological Data from Siberia and Northeast Asia on the Effect of Amanita Muscaria - Maret Saar - Journal of Ethnopharmacolgy 1991 pp. 119 Amanita Muscaria takes on a Trusty New Role - G. Hadley - Mycologist 1996 pp. 120 - 126 Isolation and characterization of a general amino acid permease from the ectomycorrhizal fungus Amanita muscaria - Nehls et al - New Phytologist 1999 pp. 127 - 134 Revisitng Wasson's Soma: Exploring the Effects of Preparation on the Chemistry of Amanita Muscaria - Kevin Feeny - Journal of Psychoactive Drugs 2010 pp. 135 - 144 Mushroom Poisoning in Infants and Children: The Amanita Pantherina/muscaria Group - D. R. Benjamin - Clinical Toxicology 1992 pp. 145 - 152 Release and dispersal of basidiospores from Amanita muscaria var . alba and their infiltration into a residence - De-Wei Li - Mycology Society 2005 pp. 153 - 166 Phylogeographic Analysis of a Boreal-Temperate Ectomycorrhizal Basidiomyte, Amanita muscaria , Suggest Forest Refugia in Alaska during the Last Glacial Maximum - Jozsef Geml et al - in Relict Species - Phylogeography and Conservation Biology, Springer 2010 pp. 167 - 178 Hallucinogenic Species in Amanita Muscaria. Determination of Muscimol and Ibotenic Acid by Ion-interaction HPLC - M. C. Gennaro et al - Universita di Torino 2014 pp. 179 - 185 Amanita Toxicosis in Two Dogs - John H. Rossmeisl Jr. et al - Journal of Veterinary Emergency and Critical Care 2006 p. 186 Peroxisome Proliferator-Activated receptot gamma: A common link for non-alchoholic fatty liver disease and colorectal cancer? - G. A. Biziulvicius - Laboratory of Immunopharmacology Vilnius 2007 pp. 187 - 199 Micorhizza helper bacterium Streptomyces Ach 505 induces differential gene expression in the ectomycorhizzal fungus Amanita muscaria - Sylvia D. Schrey et al - New Phytologist 2005 pp. 200 - 201 Mannitol in Amanita muscaria - An osmotic blood-brain barrier disruptor enhancing its Hallucinogenic action? - E. Maciejczyk et al - Medical Hypothesis 2013 pp. 202 - 216 Berengian origins and cryptic speciation events in the Fly Agaric ( Amanita muscaria ) - J. Geml et al - Molecular Ecology 2006 pp. 217 - 219 Amanita muscaria and Amanita pantherina poisoning: Two syndromes A. Vendramin et al - Toxicon 2014 pp. 220 - 239 Catching flies with Amanita muscaria : traditional recipes from Slovenia and their efficacy in the Extraction of ibotenic acid - Mateja Lumpert & Samo Kreft - Journal of Ethnopharmacolgy 2016 Psychopharmaeologia (Berl.) ,81 1-- 01 )0791( (cid:14)9 by Springer-Verlag 1970 Original snoitagitsevnI senimaonoM in the Brain under the Influence of Muscimol and Ibotenic Acid, Two Psychoactive Principles of Amanita airacsuM P. ,NISREB-GINOK P. .G ,R~SAW H. ,NNAMEGNAL and W. LICItTENSTEIGER Department of Pharmacology, University of Ziirieh, Switzerland Received February 25, 1970 Abstract. The concentrations of noradrenaline, dopamine and serotonin were measured in the brain of male albino mice and rats after intrapcritoneal injections of museimol, ibotenic acid or LSD. All three drugs induced a generalized increase of serotonin. When muscimol was administered to rats after pretreatment with p-ehlorophenylalanine, a serotonin synthesis inhibitor, the serotonin concentration was stilI increased in midbrain and hypothalamus. Muscimol also caused a reduced accumulation of 5-hydroxyindoleacetic acid in rats pretreated with probenecid. There were differences in the action of the three compounds on the catecholamine concentration. Muscimol and LSD caused a decrease of the catecholamines. Ibotenic acid increased the catecholamine concentration. Certain topographical differences were noted. The increase in the scrotonin concentration in the hypothalamns and midbrain after muscimol may be due to a reduced turnover of serotonin. An increase in sero- tonin concentration and a decrease of 5-hydroxyindolacetic acid in the rat brain are effects observed also with other psychotomimetic drugs such as LSD or psilo- cybin. Key-Words: Muscimol, Ibotenie Acid, LSD -- Monoamine Concentrations in ]3rain -- 5-Hydroxyindoleacetic Acid -- p-Chlorophenylalanine -- Probeneeid -- Turnover of Serotonin. Introduction Some hallucinogens such as Lysergid (LSD) habe been found to cause an increase in serotonin concentration and a decrease in catechol- amine concentration in the rat brain (Woolley et al., 1954; Freedman, 1961; Rosecrans et al., 1967). Two years ago, muscimol, ibotenic acid (Fig. 1) and related compounds were isolated from amanita muscaria (Eugster and Takemoto, 1967). Waser (1967) reported some pharmacological and psychotomimetic effects of these two drugs. In mice, their injection produced sympathetic effects which at least in part may be of central origin. The central control 1 aigolocamrahpohcysP ,).lreB( .loV 81 2 P. KSnig-Bersin, P. .G Waser, H. Langemann, and W. Lichtensteiger: HN-~HC~I 2 ~H--NH 2 H00C Fig. .1 Molecular structure of muscimol and ibotenic acid. muscimol = 5-amino- methyl-3-hydroxy-isoxazol, ibotenic acid = r~ acid of motor activity is also impaired with the development in mice of ataxia, catalepsy, convulsions and muscle twitches. With higher doses all treated animals showed sedation. We investigated the influence of these substances on brain mono- amines. Measurements of the monoamine concentrations in the whole brain of mice furnished only general information. More details were obtained by measuring the concentration changes in different regions of the rat brains. In order to gain some insight into the turnover of serotonin, we studied its concentration after administration of a synthe- sis inhibitor and the concentration of its metabolite, 5-hydroxy-indole- acetic acid (5-HIAA). Methods Animals. Male albino mice (20--25 g body weight) of a random bred ICl~ COBS (cesarian originated barrier sustMned) strain from Charles River Mouse Farms, and male albino rats (180--220 g body weight) of a random bred CF (Carworth Farms) strain were used. The animals were provided by the Animal Breeding Institute of the Department of Veteri- nary Medicine, University of Zfirich. Drugs. The following drugs, dissolved in saline, were administered in total volumes of 0.1 ml/100 g: museimol 3 mg/kg i.p. ibotenic acid 16 mg/kg i.p. LSD 10 mg/kg i.p. p-chlorophenylalanine 300 mg/kg i.p. probenecid 300 mg/kg p.o. 0.9 ~ NaC1 1 ml/kg i.p. (control animals) Brain Sectioning. After decapitation the rat brains were quickly removed and cut just behind the medulla obiongata. The cerebellum, senimaonoM in Brain under Influence of Muscimol and Ibotenic Acid 3 I I d P*M ,, b/ir - I I la Fig.2. Sagittal section of rat brain (K6nig and Klippel, .)3691 The dotted lines (a, b, c, d) represent frontal cuttings. BO bnlbus olfactorius; H Y hypothalamns with median thalamus and medial hippocampus; MI midbrain; P -k M pons and medulla oblongata; CB cerebellum i ; el ~f Fig.3. Frontal section of rat brain (KSnig and Klippel, 1963). The dotted lines represent sagRtal cuttings ,e( ]). HI hippocampus; H habenula; ruTH median thalamus; FMG fasciculus mamillothalamicus; F columna fornicis; I infundibulum; CAI capsula interna; Cp nucleus caudatus putamen; Am amygdala; To tractus opticus. .1 "Forebrain" contains cortex, striatum, amygdala and lateral parts of thalamus. 2. "Hypothalamus" contains hypothalamus, median thalamus and medial hippocampus the olfactory bulb and the pineal gland were discarded. Amine deter- minations were performed in four brain areas: Medulla oblongata -J- pons, midbrain, hypothalamus -A median thalamus, remaining forebrain. The position of the various cuts is given in Figs. 2 and 3. Fluorimetric Determination. Noradrenaline was determined according to Bertler et al. (1958), dopamine according to Carlsson and Waldeck (1958) and 5-hydroxytryptamine according to Udenfriend et al. (1958). 1' 4 P. KSnig-Bersin, P. G. Waser, H. Langemann, and W. Lichtensteiger: Table .1 Monoamine concentrations (ng/g /resh tissue) in the mouse brain two hours alter the i.p. injection o/16 mg/kg ibotenic acid, 3 mg/kg muscimol or 10 mg/kg LSD Ibotenic acid Muscimol LSD (cid:127) (n) 4-S.D. (n) ~=S.D. (n) NA T 539(cid:127) )5( 4474-44 )3( 2494- 76 )5( C 4854-55 (a) 4744-47 (a) 2694- 76 )7( DA T 4264-30 )4( 4324-51 )3( 519(cid:127) )7( C 3544-37 )4( 3674-34 )3( 6034-100 )7( p < 0,0025 o~ ~ 0.05 5-HT T 3634-77 (11) 399(cid:127) )8( 3424- 15 (3) C 3684-81 )8( 3604-91 )6( 3004- 25 )3( p_< 0.10 p_< 0.05 Abbreviations/or Table 1--4. S.D. standard deviation (n) number of experiments each with 4--5 animals T mean concentration in the test brain tissue C mean concentration in the control brain tissue P confidence coefficient FB forebrain HY hypothalamus MI midbrain P-~ M pens and medulla oblongata. with slight modifications (H/~ggendal, 1962). We added 0.1 ml of 20/0 ascorbie acid and 0,2 ml of 10~ EDTA to 10 ml aqueous solution. 5-HIAA was estimated fluorimetrieally as described by Roos (1962) and Sharman and Smith (1962). In the experiments on mice, 4 whole brains were pooled, whereas in the studies on rats 5 brain sections were used for one determination. Care was taken to start the experiments always at the same time of the day. The average recovery of the monoamines which were added to tissue homogenate and carried through the pro- cedures ranged between 85 and 95 percent. The values in the tables are corrected for this recovery. Statistical Analysis. Differences of the fluorescence intensity between test and control samples were analysed by means of the F-test and t-test comparison (Doerffel, 1965). Differences between the means of treated and control animals are considered to be significant ff the confidence coefficient is 95~ (p < 0.05) or more. Results There is some similarity between the effects of museimol and LSD on the overall monoamine concentration in the mouse brain (Table 1). l~onoamines in Brain under Influence of Muscimol and Ibotenic Acid 5 Table 2. Monoamlne concentrations in/our di//erent regions o[ rat brain (ng/g /resh tissue) two hours after the in~ection o[ ibotenic acid (16 mg/kg ).~1.i EB H Y MI P + M (cid:127) (n) (cid:127) (n) iS.D. (n) +S.D. (n) AN~ T 1954- 84 )4( 7524-306 )4( 10564-428 )4( 513-4-179 )4( C 229+102 )8( 531+237 )6( 542+161 )7( 404+110 )6( p< 0.10 p_< 0.01 I)A T 3664- 77 )4( 7684-209 )4( 4654- 43 )4( 3904-245 )4( G 384(cid:127) 86 )5( 5744-146 )5( 3984-141 )6( 1774- 30 )5( p_< 0.10 p< 0.05 5-HT T 2944- 68 )5( 721(cid:127) 82 )5( 804(cid:127) 47 )4( 4544- 87 )5( C 2594- 70 )7( 612(cid:127) )9( 6854-101 )9( 4134- 83 )9( p_< 0.05 p~< 0.025 p_< 0.10 Table 3. Monoamine concentrations in/our di//erent regions o/ rat brain (ng/g /resh tissue) two hours alter the injection o/ muscimol (3 mg/kg i.p.) FB H Y MI P + M 4-S.D. (n) 4-S.D. (n) 4-S.D. )n( 4-S.D. (n) NA T 2004- 49 )5( 6454-250 )5( 3924-205 )5( 3894-122 )5( C 2414- 44 )4( 7654-315 )5( 4304- 18 )5( 5544-103 )5( p ~ 0.05 DA T 5484-209 )5( 9614-234 )4( 5524-389 )5( 393=[=104 )4( C 8094-179 )5( 1245-4-339 )4( 7724-334 )4( 3264-106 )4( p~< 0.05 5-HT T 3564- 85 )5( 8194-321 )4( 8084-128(5) 5604-196 )5( C 275+ 43 )6( 670+248 )4( 706+119 )5( 464+139 )5( p_< 0.05 The serotonin concentration increased and the noradrenMine concentra- tion decreased. However the dopamine concentration increased after muscimol ill contrast to a decrease after LSD. After ibotenie acid an increase was observed in noradrenMine and dopamine concentrations in the mouse brain, whereas the serotonin concentration did not change. The relatively small changes in mono- amine concentration in the mouse brain could originate from large chan- ges in small brain areas. Therefore, the influence of mnscimol, ibotenie acid and LSD was investigated in four different regions of the rat brain (Tables 2 and 3). Following the injection of ibotenic acid the noradrenaline content was markedly increased in the hypothalamus, midbrain and pons 6 P. KSnig-Bersin, P. G. Waser, H. Langemann, and W. Lichtensteiger: gn g/TH-5 tomics~ um+APC-p e~_F t A>FC-p lOl = (cid:12)9 ~.L "~ 0 I I ; BY 001 0 I I ! i ~M tO0 0 I I I P,M 100 I I Fig.4. Serotoain concentration in rat brain one, two, four and six hours after injec- tion of muscimol 3( mg/kg i.p.). The animals were pretreated with p-chlorophenyl- alanine (300 mg/kg i.p.) 84 hours before the muscimol injection. FB forebrain; MI midbrain; HY hypothalamus; P + M pons and medulla oblongata ~- medulla oblongata (Table 2). The dopamlne concentration was in- creased in the hypothalamus and pons -~ medulla oblongata, and showed a tendency to rise in the midbrain and to fall in the forebrain. Serotonin concentrations increased especially in hypothalamus and midbrain. After the injection of muscimo] the noradrenaline concentration was markedly lowered in pons and medulla ohlongata (Table 3), and a similar tendency was found in all other regions. Dopamine decreased markedly in the forebrain. A slight decrease was also observed in the hypothalamus and midbrain, with an increase in pons and medulla oblongata. Serotonin levels were distinctly increased in all parts, but the change was only significant in the forebrain. The generalized increase of serotonin induced by muscimol, iboterdc acid was well as by LSD suggested further investigations. 48 hours after administration of p-chlorophenylalanine, which inhibits the 5-I~T syn-

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A compendium of journal articles concerning the hallucinogenic properties of the Amanita muscaria mushroom and related species. Includes: pp. 6 - 15 Monoamines in the Brain under the Influence of Muscimol and Ibotenic Acid, Two Psychoactive Principles of Amanita Muscaria P. Konig-Persin et al - Psyc
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