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Metabolic Brain Disease
Published in: Metabolic Brain Disease 2/2014

01-06-2014 | Original Paper

Effects of acute and chronic inhalation of paint thinner in mice: behavioral and immunohistochemical study

Authors: Karim Fifel, Mohamed Bennis, Saâdia Ba-M’hamed

Published in: Metabolic Brain Disease | Issue 2/2014

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Abstract

Abuse of volatile inhalants has become a worldwide issue mainly among adolescents of low income social class. Acute and chronic exposure to these substances results in serious neurological and behavioral impairments. Although real exposure consists largely of simultaneous inhalation of multiple solvents, the vast majority of basic research studies have evaluated the actions of a single volatile component leaving the behavioral and neuronal effects of chemical mixture not fully understood. In this study, we investigated the acute behavioral effects of 300, 450 and 600 ppm of paint thinner inhalation on anxiety, locomotor activity and spatial memory. Additionally, the cognitive impairments related to chronic exposure of the same concentrations of thinner for 45 days were assessed. To understand the neuronal correlates of acute exposure to thinner, we used c-Fos immunohistochemistry as an endogenous marker of neuronal activation following 600 ppm of thinner. The results reveal that (i) chronically thinner exposed mice showed cognitive deficits in Morris water maze and object recognition tasks; (ii) acute inhalation of thinner induces a wide range of behavioral changes. These changes include an anxiolytic effect toward the aversive environmental bright light and a dose dependent effect on explorative locomotion. The wide range of behavioral alterations induced by acute thinner inhalation is consistent with the widespread distribution of thinner-induced c-Fos expression in multiple brain structures.
Literature
Bale AS, Tu Y, Carpenter-Hyland EP, Chandler LJ, Woodward JJ (2005) Alterations in glutamatergic and gabaergic ion channel activity in hippocampal neurons following exposure to the abused solvent toluene. Neuroscience 130:197–206PubMedCrossRef
Baydas G, Ozveren F, Akdemir I, Tuzcu M, Yasar A (2005a) Learning and memory deficits in rats induced by chronic thinner exposure are reversed by melatonin. J Pineal Res 39:50–56PubMedCrossRef
Baydas G, Ozveren F, Tuzcu M, Yasar A (2005b) Effects of thinner exposure on the expression pattern of neural cell adhesion molecules, level of lipid peroxidation in the brain and cognitive function in rats. Eur J Pharmacol 512:181–187PubMedCrossRef
Beck CHM, Fibiger HC (1995) Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fos: with and without diatzepam pretreatment. J Neurosci 15:709–720PubMed
Beckley JT, Woodward JJ (2013) Volatile solvents as drugs of abuse: focus on the cortico-mesolimbic circuitry. Neuropsychopharmacology Aug 19. [Epud ahead of print]
Bittencourt JC, Sawchenko PE (2000) Do centrally administered neuropeptides access cognate receptors? AN analysis in the central corticotropin-releasing factor system. J Neurosci 20:1142–1156PubMed
Blokhina EA, Dravolina OA, Bespalov AY, Balster RL, Zvartau EE (2004) Intravenous self-administration of abused solvents and anesthetics in mice. Eur J Pharmacol 485:211–218PubMedCrossRef
Bogdanova OV, Kanekar S, D’Anci KE, Renshaw PF (2013) Factors influencing behavior in the forced swim test. Physiol Behav 118:227–239PubMedCrossRef
Boor JW, Hutrig HI (1977) Permanent cerebellar ataxia after exposure to toluene. Ann Neurol 2:440–442PubMedCrossRef
Bouwknecht JA, Spiga F, Staub DR, Hale MW, Shekhar A, Lowry CA (2007) Differential effects of exposure to low-light or high-light open-field on anxiety-related behaviors: relationship to c-Fos expression in serotonergic and non-serotonergic neurons in the dorsal raphe nucleus. Brain Res Bull 72:32–43PubMedCentralPubMedCrossRef
Bowen SE, Balster RL (1998) A direct comparison of inhalant effects on locomotor activity and schedule-controlled behavior in mice. Exp Clin Psychopharmacol 6:235–247PubMedCrossRef
Bowen SE, Batis JC, Paez-Martinez N, Cruz SL (2006) The last decade of solvent research in animal models of abuse: mechanistic and behavioral studies. Neurotoxicol Teratol 28:636–647PubMedCrossRef
Bowen SE, Wiley JL, Balster RL (1996) The effects of abused inhalants on mouse behavior in an elevated plus-maze. Eur J Pharmacol 312:131–136PubMedCrossRef
Byrne A, Kirby B, Zibin T, Ensminger S (1991) Psychiatric and neurological effects of chronic solvent. Can J Psychiatry 36:735–738PubMed
Choi DC, Furay AR, Evanson NK, Ostrander MM, Ulrich-Lai YM, Herman JP (2007) Bed nucleus of the stria terminalis subregions differentially regulate hypothalamic-pituitary-adrenal axis activity: implications for the integration of limbic inputs. J Neurosci 27:2025–2034PubMedCrossRef
Compaan JC, Groenink L, Jvd G, Maes RAA, Olivier B (1996) 5-HT1A receptor agonist flesinoxan enhances Fos immuno- reactivity in rat central amygdala, bed nucleus of the stria terminalis and hypothalamus. Eur J Neurosci 8:2340–2347PubMedCrossRef
Cruz SL, Mirshahi T, Thomas B, Balster RL, Woodward JJ (1998) Effects of the abused solvent toluene on recombinant N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors expressed in Xenopus oocytes. J Pharmacol Exp Ther 286:334–340PubMed
Curran EJ, Akil H, Watson SJ (1996) Psychomotor stimulant and opiate-induced c-fos mRNA expression patterns in the rat forebrain: comparisons between acute drug treatment and a drug challenge in sensitized animals. Neurochem Res 21:1425–1435PubMedCrossRef
Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28:771–784PubMedCrossRef
Davis M, Rainnie D, Cassell M (1994) Neurotransmission in the rat amygdala related to fear and anxiety. Trends Neurosci 5:208–214CrossRef
Davis M, Shi C (1999) The extended amygdala: are the central nucleus of the amygdala and the bed nucleus of the stria terminalis differentially involved in fear versus anxiety? Ann N Y Acad Sci 877:281–291PubMedCrossRef
De Bruin JP, Sanchez-Santed F, Heinsbroek RP, Donker A, Postmes P (1994) A behavioural analysis of rats with damage to the medial prefrontal cortex using the Morris water maze: evidence for behavioural flexibility, but not for impaired spatial navigation. Brain Res 652:323–333PubMedCrossRef
Dingwall KM, Maruff P, Fredrickson A, Cairney S (2011) Cognitive recovery during and after treatment for volatile solvent abuse. Drug Alcohol Depend 118:180–185PubMedCrossRef
Fendt M, Endres T, Apfelbach R (2003) Temporary inactivation of the bed nucleus of the stria terminalis but not of the amygdala blocks freezing induced by trimethylthiazoline, a component of fox feces. J Neurosci 23:23–28PubMed
Fornazzari L, Wilkinson DA, Kapur BM, Carlen PL (1983) Cerebellar, cortical and functional impairment in toluene abusers. Acta Neurol Scand 67:319–329PubMedCrossRef
Gmaz JM, Yang L, Ahrari A, McKay BE (2012) Binge inhalation of toluene vapor produces dissociable motor and cognitive dysfunction in water maze tasks. Behav Pharmacol 23:669–677PubMedCrossRef
Gotohda T, Tokunaga I, Kubo S (2005) Toluene inhalation-induced adrenocortical hypertrophy and endocrinological changes in rat. Life Sci 76:1929–1937PubMedCrossRef
Grabski DA (1961) Toluene sniffing producing cerebellar degeneration. Am J Psychiatry 118:461–462PubMed
Harlan RE, Garcia MM (1998) Drugs of abuse and immediate early genes in the forebrain. Mol Neurobiol 16:221–267PubMedCrossRef
Hathaway GJ, Proctor NH (2004) Proctor and Hughes’ chemical hazards of the workplace, 5th edn. Wiley, Hoboken, pp 681–682CrossRef
Hormes JT, Filley CM, Rosenberg NL (1986) Neurologic sequelae of chronic solvent vapour abuse. Neurology 36:698–702PubMedCrossRef
Kishi R, Harabuchi I, Katakura Y, Ikeda T, Miyake H (1993) Neurobehavioral effects of chronic occupational exposure to organic solvents among Japanese industrial painters. Environ Res 62:303–313PubMedCrossRef
Korbo L, Ladefoged O, Lam HR, Ostergaard G, West MJ, Arlien-Soborg P (1996) Neuronal loss in hippocampus in rats exposed to toluene. Neurotoxicology 17:359–366PubMed
Kurtzman TL, Otsuka KN, Wahl RA (2001) Inhalant abuse by adolescents. J Adolesc Health 28:170–180PubMedCrossRef
Lazar RB, Ho SU, Melen O, Daghestani AN (1983) Multifocal central nervous system damage caused by toluene abuse. Neurology 33:1337–1340PubMedCrossRef
Lo PS, Chen HH (2005) Immunohistochemical localization of toluene-induced c-Fos protein expression in the rat brain. Toxicol Lett 157:151–160PubMedCrossRef
Marsolek MR, White NC, Litovitz TL (2010) Inhalant abuse: monitoring trends by using poison control data, 1993–2008. Pediatrics 125:906–913PubMedCrossRef
Martínez-Alfaro M, Alcaraz-Contreras Y, Cárabez-Trejo A, Leo-Amador GE (2011) Oxidative stress effects of thinner inhalation. Indian J Occup Environ Med 15:87–92PubMedCentralPubMedCrossRef
Miyagawa M, Honma T, Sato M (1995) Effects of subchronic exposure to toluene on working and reference memory in rats. Neurotoxicol Teratol 17:657–664PubMedCrossRef
Miyata H, Kono J, Ushijima S, Yanagita T, Miyasato K, Fukui K (2004) Clinical features of nicotine dependence compared with those of alcohol, methamphetamine, and inhalant dependence. Ann N Y Acad Sci 1025:481–488PubMedCrossRef
Morris RG, Garrud P, Rawlins JN, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683PubMedCrossRef
Paxinos G and Franklin KBJ (2001) The mouse brain in stereotaxic coordinates 2nd edn. (Elsevier Academic Press)
Perit KE, Gmaz JM, Caleb Browne JD, Matthews BA, Dunn MB, Yang L, Raaphorst T, Mallet PE, McKay BE (2012) Distribution of c-Fos immunoreactivity in the rat brain following abuse-like toluene vapor inhalation. Neurotoxicol Teratol 34:37–46PubMedCrossRef
Pitkanen A, Savander V, LeDoux JE (1997) Organization of intraamygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala. Trends Neurosci 20:517–523PubMedCrossRef
Raines DE, Gioia F, Claycomb RJ, Stevens RJ (2004) The N-methyl-Daspartate inhibitory potencies of aromatic inhaled drugs of abuse: evidence for modulation by cation-pi interactions. J Pharmacol Exp Ther 311:14–21PubMedCrossRef
Ridenour TA, Bray BC, Cottler LB (2007) Reliability of use, abuse, and dependence of four types of inhalants in adolescents and young adults. Drug Alcohol Depend 91:40–49PubMedCentralPubMedCrossRef
Riegel AC, Ali SF, French ED (2003) Toluene-induced locomotor activity is blocked by 6-hydroxydopamine lesions of the nucleus accumbens and the mGluR2/3 agonist LY379268. Neuropsychopharmacology 28:1440–1447PubMedCrossRef
Riegel AC, French ED (1999) Acute toluene induces biphasic changes in rat spontaneous locomotor activity which are blocked by remoxipride. Pharmacol Biochem Behav 62:399–402PubMedCrossRef
Riegel AC, Zapata A, Shippenberg TS, French ED (2007) The abused inhalant toluene increases dopamine release in the nucleus accumbens by directly stimulating ventral tegmental area neurons. Neuropsychopharmacology 32:1558–1569PubMedCrossRef
Ron MA (1986) Volatile substance abuse: a review of possible long-term neurological, intellectual and psychiatric sequelae. Ann Neurol 148:235–246
Ryabinin AE, Criado JR, Henriksen SJ, Bloom FE, Wilson MC (1997) Differential sensitivity of c-Fos expression in hippocampus and other brain regions to moderate and low doses of alcohol. Mol Psychiatry 2:32–43PubMedCrossRef
Salminen O, Lahtinen S, Ahtee L (1996) Expression of Fos protein in various rat brain areas following acute nicotine and diazepam. Pharmacol Biochem Behav 54:241–248PubMedCrossRef
Schilstrom B, De Villiers S, Malmerfelt A, Svensson TH, Nomikos GG (2000) Nicotine-induced Fos expression in the nucleus accumbens and the medial prefrontal cortex of the rat: role of nicotinic and NMDA receptors in the ventral tegmental area. Synapse 36:314–321PubMedCrossRef
Stone EA, Zhang Y (1995) Adrenoceptor antagonists block c-fos response to stress in the mouse brain. Brain Res 694:279–286PubMedCrossRef
Streicher HZ, Gabow PA, Moss AH, Kono D, Kaehny WD (1981) Syndromes of toluene sniffing in adults. Ann Intern Med 94:758–762PubMedCrossRef
Sun N, Cassell MD (1993) Intrinsic GABAergic neurons in the rat central extended amygdala. J Comp Neurol 330:381–404PubMedCrossRef
Takagi M, Lubman DI, Cotton S, Fornito A, Baliz Y, Tucker A, Yücel M (2011) Executive control among adolescent inhalant and cannabis users. Drug Alcohol Rev 30:629–637PubMedCrossRef
Takao K, Miyakawa T (2006) Light/dark transition test for mice. J Vis Exp 13:104
Thiriet N, Zwiller J, Ali SF (2001) Induction of the immediate early genes egr-1 and c-fos by methamphetamine in mouse brain. Brain Res 919:31–40PubMedCrossRef
Vertes RP (2006) Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience 142:1–20PubMedCrossRef
Von Euler M, Pham TM, Hillefors M, Bjelke B, Henriksson B, von Euler G (2000) Inhalation of low concentrations of toluene induces persistent effects on a learning retention task, beam-walk performance, and cerebrocortical size in the rat. Exp Neurol 163:1–8CrossRef
Walker DL, Davis M (1997) Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear. J Neurosci 17:9375–9383PubMed
Wang JD, Chen JD (1993) Acute and chronic neurological symptoms among paint workers exposed to mixtures of organic solvents. Environ Res 61:107–116PubMedCrossRef
Wiley JL, Fagalde RE, Buhler KG, LaVecchia KL, Balster RL (2002) Evaluation of 1,1,1-trichloroethane and flurothyl locomotor effects following diazepam treatment in mice. Pharmacol Biochem Behav 71:163–169PubMedCrossRef
Williams JM, Stafford D, Steketee JD (2005) Effects of repeated inhalation of toluene on ionotropic GABAA and glutamate receptor subunit levels in rat brain. Neurochem Int 46:1–10PubMedCrossRef
Yücel M, Takagi M, Walterfang M, Lubman DI (2008) Toluene misuse and long-term harms: a systematic review of the neuropsychological and neuroimaging literature. Neurosci Biobehav Rev 32:910–926PubMedCrossRef
Zubaran C, Foresti K, Thorell MR, Franceschini P, Homero W (2010) Depressive symptoms in crack and inhalant users in Southern Brazil. J Ethn Subst Abus 9:221–236CrossRef
Metadata
Title
Effects of acute and chronic inhalation of paint thinner in mice: behavioral and immunohistochemical study
Authors
Karim Fifel
Mohamed Bennis
Saâdia Ba-M’hamed
Publication date
01-06-2014
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 2/2014
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-013-9449-4

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