Skip to main content

Advertisement

SpringerLink
Log in

Cross-Generational trans Fat Consumption Favors Self-Administration of Amphetamine and Changes Molecular Expressions of BDNF, DAT, and D1/D2 Receptors in the Cortex and Hippocampus of Rats

  • Original Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Amphetamine (AMPH) is an addictive psychostimulant drug whose use has been related to neurotoxicity. Experimentally, AMPH increases anxiety-like symptoms, showing addictive properties. In the last decades, the growing consumption of processed foods has provided an excess of saturated and trans fats in detriment of essential fatty acids, which may modify the lipid profile of brain membranes, thus modifying its permeability and dopaminergic neurotransmission. Here, we assessed the influence of brain incorporation of different fatty acids (FA) on AMPH self-administration. Three groups of young male rats were orally supplemented from weaning with a mixture of soybean oil (SO, rich in n-6 FA) and fish oil (FO, rich in n-3 FA), hydrogenated vegetable fat (HVF, rich in trans fatty acids—TFA), or water (control group). These animals were born from dams that were supplemented with the same fat from pregnancy to lactation. Anxiety-like symptoms and locomotor index were assessed in elevated plus maze and open-field (OF), respectively, while brain molecular expressions of dopaminergic receptors, dopamine transporter (DAT), and BDNF were determined in the cortex and hippocampus. HVF increased the frequency of AMPH self-administration and was associated with reinforcement and withdrawal signs as observed by increased anxiety-like symptoms. Contrarily, SO/FO decreased these parameters. Increased BDNF protein together with decreased DAT expression was observed in the hippocampus of HVF group. Based on these findings, our study points to a harmful influence of trans fats on drug addiction and craving symptoms, whose mechanism may be related to changes in the dopaminergic neurotransmission.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Acar N, Chardigny JM, Darbois M, Pasquis B, Sébédio JL (2003) Modification of the dopaminergic neurotransmitters in striatum, frontal cortex and hippocampus of rats fed for 21 months with trans isomers of α-linolenic acid. Neurosci Res 45(4):375–382

    Article  CAS  PubMed  Google Scholar 

  • Amara SG, Kuhar MJ (1993) Neurotransmitter transporters: recent progress. Annu Rev Neurosci 16:73–93

    Article  CAS  PubMed  Google Scholar 

  • Arcand J, Scourboutakos MJ, Au JTC, Abbe MRL (2014) Trans fatty acids in the canadian food supply: an updated analysis. Am J Clin Nutr 100(4):1116–1123

    Article  CAS  PubMed  Google Scholar 

  • Baquet ZC, Bickford PC, Jones KR (2005) Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci 25(26):6251–6259

    Article  CAS  PubMed  Google Scholar 

  • Beaglehole R, Bonita R, Horton R, Adams C, Alleyne G, Asaria P, Baugh V, Bekedam H, Billo N, Casswell S (2011) Priority actions for the non-communicable disease crisis. Lancet 377(9775):1438–1447

    Article  PubMed  Google Scholar 

  • Beninger RJ, Hoffman DC, Mazurski EJ (1989) Receptor subtype-specific dopaminergic agents and conditioned behavior. Neurosci Biobehav Rev 13(2–3):113–122

    Article  CAS  PubMed  Google Scholar 

  • Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37(8):911–917

    Article  CAS  PubMed  Google Scholar 

  • Bourre JM, Francois M, Youyou A, Dumont O, Piciotti M, Pascal G, Durand G (1989) The effects of dietary alphalinolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr 119(12):1880–1892

    CAS  PubMed  Google Scholar 

  • Bousquet M, Gibrat C, Saint-Pierre M, Julien C, Calon F, Cicchetti F (2009) Modulation of brain-derived neurotrophic factor as a potential neuroprotective mechanism of action of omega-3 fatty acids in a parkinsonian animal model. Prog Neuropsychopharmacol Biol Psychiatry 33(8):1401–1408

    Article  CAS  PubMed  Google Scholar 

  • Bowyer JF, Ali S (2006) High doses of methamphetamine that cause disruption of the blood–brain barrier in limbic regions produce extensive neuronal degeneration in mouse hippocampus. Synapse 60(7):521–532

    Article  CAS  PubMed  Google Scholar 

  • Buydens-Branchey L, Branchey M, Mcmakin D (2003) Polyunsaturated fatty acid status and aggression in cocaine addicts. Drug Alcohol Depend 71(3):319–323

    Article  CAS  PubMed  Google Scholar 

  • Buydens-Branchey L, Branchey M, Hibbeln JR (2008) Associations between increases in plasma n-3 polyunsaturated fatty acids following supplementation and decreases in anger and anxiety in substance abusers. Prog Neuropsychopharmacol Biol Psychiatry 32:568–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chalon S (2006) Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukot Essent Fatty Acids 75(4–5):259–269

    Article  CAS  PubMed  Google Scholar 

  • Chen CT, Green JT, Orr SK, Bazinet RP (2008) Regulation of brain polyunsaturated fatty acid uptake and turnover. Prostaglandins Leukot Essent Fatty Acids 79(3–5):85–91

    Article  CAS  PubMed  Google Scholar 

  • Cohen H, Liu T, Kozlovsky N et al (2012) The Neuropeptide Y (NPY)-ergic system is associated with behavioral resilience to stress exposure in an animal model of post-traumatic stress disorder. Neuropsychopharmacology 37:350–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feltstein MW, See RE (2008) The neurocircuitry of addiction: an overview. Br J Pharmacol 154:261–274

    Article  Google Scholar 

  • Ferraz AC, Delattre AM, Almendra RG, Sonagli M, Borges C, Araujo P, Andersen ML, Tufik S, Lima MM (2011) Chronic n-3 fatty acids supplementation promotes beneficial effects on anxiety, cognitive and depressive-like behaviors in rats subjected to a restraint stress protocol. Behav Brain Res 219(1):116–122

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Pinilla F (2008) The influences of diet and exercise on mental health through hormesis. Ageing Res Rev 7(1):49–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonçalves J, Baptista S, Silva AP (2014) Psychostimulants and brain dysfunction: a review of the relevant neurotoxic effects. Neuropharmacology 87:135–149

    Article  PubMed  Google Scholar 

  • Green JT, Orr SK, Bazinet RP (2008) The emerging role of group vi calcium in dependent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids. J Lipid Res 49(5):939–944

    Article  CAS  PubMed  Google Scholar 

  • Hartman L, Lago BC (1973) A rapid preparation of fatty methyl esters from lipids. Lab Pract 22(6):475–477

    CAS  PubMed  Google Scholar 

  • Henderson ND, Turri MG, Defries JC, Flint J (2004) QTL analysis of multiple behavioral measures of anxiety in mice. Behav Genet 34(3):267–293

    Article  PubMed  Google Scholar 

  • Hlavacova N, Bakos J, Jezova D (2010) Eplerenone, a selective mineralocorticoid receptor blocker, exerts anxiolytic effects accompanied by changes in stress hormone release. J Psychopharmacol 24(5):778–779

    Article  Google Scholar 

  • Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350(6315):230–232

    Article  CAS  PubMed  Google Scholar 

  • Hyman SE, Malenka RC, Nestler EJ (2006) Neural mechanisms of addiction: the role of reward-related learning and memory. Ann Rev Neurosci 29:565–598

    Article  CAS  PubMed  Google Scholar 

  • Jackson DM, Westlind-Danielsson A (1994) Dopamine receptors: molecular biology, biochemistry and behavioral aspects. Pharmacol Ther 64(2):291–369

    Article  CAS  PubMed  Google Scholar 

  • Jump DB (2002) Dietary polyunsaturated fatty acids and regulation of gene transcription. Curr Opin Lipidol 13(2):155–164

    Article  CAS  PubMed  Google Scholar 

  • Kerr DS, Bevilaqua LR, Bonini JS, Rossato JI, Köhler CA, Medina JH, Izquierdo I, Cammarota M (2005) Angiotensin II blocks memory consolidation through an AT2 receptor-dependent mechanism. Psychopharmacology 179(3):529–535

    Article  CAS  PubMed  Google Scholar 

  • Kodas E, Page G, Zimmer L, Vancassel S, Guilloteau D, Durand G, Chalon S (2002) Neither the density nor function of striatal dopamine transporters were influenced by chronic n-3 polyunsaturated fatty acid deficiency in rodents. Neurosci Lett 321(1–2):95–99

    Article  CAS  PubMed  Google Scholar 

  • Kuhn FT, Kr Roversi, Antoniazzi CTD, Pase CS, Trevizol F, Barcelos RCS, Dias VT, Roversi K, Boufleur N, Benvegnú DM, Piccolo J, Emanuelli T, Bürger ME (2013) Influence of trans fat and omega-3 on the preference of psychostimulant drugs in the first generation of young rats. Pharmacol Biochem Behav 110:58–65

    Article  CAS  PubMed  Google Scholar 

  • Kuhn FT, Trevizol F, Dias VT, Barcelos RCS, Pase CS, Kr Roversi, Antoniazzi CTD, Roversi K, Boufleur N, Benvegnú DM, Piccolo J, Emanuelli T, Bürger ME (2015) Toxicological aspects of trans fat consumption over two sequential generations of rats: oxidative damage and preference for amphetamine. Toxicol Lett 232(1):58–67

    Article  CAS  Google Scholar 

  • Lambert EJ (2006) Trans fatty acids and health—what is the evidence? J Heia 13:6–11

    Google Scholar 

  • Lang UE, Sander T, Lohoff FW, Hellweg R, Bajbouj M, Winterer G, Gallinat J (2007) Association of the met66 allele of brain-derived neurotrophic factor (BDNF) with smoking. Psychopharmacology 190(4):433–439

    Article  CAS  PubMed  Google Scholar 

  • Laurent RST, Helm SR, Glenn MJ (2013) Reduced cocaine-seeking behavior in heterozygous BDNF knockout rats. Neurosci Lett 544:94–99

    Article  Google Scholar 

  • Leão RM, Cruz FC, Carneiro-de-Oliveira PE, Rossetto DB, Valentini SR, Zanelli CF, Planeta CS (2013) Enhanced nicotine-seeking behavior following pre-exposure to repeated cocaine is accompanied by changes in BDNF in the nucleus accumbens of rats. Pharmacol Biochem Behav 104:169–176

    Article  PubMed  Google Scholar 

  • Maldonado R, Robledo P, Chover AJ, Caine SB, Koob GF (1993) D1 dopamine receptors in the nucleus accumbens modulate cocaine self-administration in the rat. Pharmacol Biochem Behav 45(1):239–242

    Article  CAS  PubMed  Google Scholar 

  • Meng M, Zhao X, Dang Y, Ma J, Li L, Gu S (2013) Region-specific expression of brain-derived neurotrophic factor splice variants in morphine conditioned place preference in mice. Brain Res 1519:53–62

    Article  CAS  PubMed  Google Scholar 

  • Missale C, Nash SR, Robinson SW, Jaber M, Caron MC (1998) Dopamine receptors: from structure to function. Physiol Rev 78(1):189–225

    CAS  PubMed  Google Scholar 

  • Montgomery K (1955) The relation between fear induced by novel stimulation and exploratory behavior. J Comp Physiol Psychol 48(4):254–260

    Article  CAS  PubMed  Google Scholar 

  • Naef L, Srivastava L, Gratton A, Hendrickson H, Owens SM, Walker CD (2008) Maternal high fat diet during the perinatal period alters mesocorticolimbic dopamine in the adult rat offspring: reduction in the behavioral responses to repeated amphetamine administration. Psychopharmacology 197(1):83–94

    Article  CAS  PubMed  Google Scholar 

  • National Institute on Drug Abuse—NIDA (2014) Stimulant ADHD medications. U.S. Department of Health and Human Services 1–2

  • Panlilio LV, Goldberg SR (2007) Self-administration of drugs in animals and humans as a model and an investigative tool. Addiction 102(12):1863–1870

    Article  PubMed  PubMed Central  Google Scholar 

  • Pase CS, Kr Roversi, Trevizol F, Roversi K, Kuhn FT, Schuster AJ, Vey LT, Dias VT, Barcelos RCS, Piccolo J, Emanuelli T, Bürger ME (2013) Influence of perinatal trans fat on behavioral responses and brain oxidative status of adolescent rats acutely exposed to stress. Neuroscience 247:242–252

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Elsevier, Amsterdam

    Google Scholar 

  • Phillips GD, Robbins TW, Everitt BJ (1994) Bilateral intra-accumbens self-administration of d-amphetamine: antagonism with intra-accumbens sch 23390 and sulpiride. Psychopharmacology 114(3):477–485

    Article  CAS  PubMed  Google Scholar 

  • Puglisi-Allegra S, Kempf E, Schleef C, Cabib S (1991) Repeated stressful experiences differently affect brain dopamine receptor subtypes. Life Sci 48(13):1263–1268

    Article  CAS  PubMed  Google Scholar 

  • Rodgers RJ, Dalvi A (1997) Anxiety, defence and the elevated plus-maze. Neurosci Biobehav Rev 21(6):801–810

    Article  CAS  PubMed  Google Scholar 

  • Sandtner W, Schmid D, Schicker K et al (2013) A quantitative model of amphetamine action on the serotonin transporter. Br J Pharmacol 171(4):1007–1018

    Article  Google Scholar 

  • Schultz W (2002) Getting formal with dopamine and reward. Neuron 36:241–263

    Article  CAS  PubMed  Google Scholar 

  • Shahbazi M, Moffett AM, Williams BF, Frantz KJ (2008) Age- and sex-dependent amphetamine self-administration in rats. Psychopharmacology 196(1):71–81

    Article  CAS  PubMed  Google Scholar 

  • Shen YL, Chang TY, Chang YC, Tien HH, Yang FC, Wang PY, Liao RM (2014) Elevated BDNF mRNA expression in the medial prefrontal cortex after d-amphetamine reinstated conditioned place preference in rats. Neuroscience 263:88–95

    Article  CAS  PubMed  Google Scholar 

  • Sitte HH, Freissmuth M (2010) The reverse operation of Na +/Cl—coupled neurotransmitter transporters—why amphetamines take two to tango. J Neurochem 112:340–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sitte HH, Freissmuth M (2015) Amphetamines, new psychoactive drugs and the monoamine transporter cycle. Trends Pharmacol Sci 36:41–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sitte HH, Huck S, Reither H et al (1998) Carrier-mediated release, transport rates, and charge transfer induced by amphetamine, tyramine, and dopamine in mammalian cells transfected with the human dopamine transporter. J Neurochem 71:1289–1297

    Article  CAS  PubMed  Google Scholar 

  • Substance Abuse and Mental Health Services Administration—SAMHSA (2014) Results from the 2013 national survey on drug use and health: summary of national findings. U.S. Dep. Health Human Serv. 1–184

  • Sulzer D (2011) How addictive drugs disrupt presynaptic dopamine neurotransmission. Neuron 69:628–649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teixeira AM, Pase CS, Boufleur N, Roversi K, Barcelos RCS, Benvegnú DM, Segat HJ, Dias VT, Reckziegel P, Trevizol F, Dolci GS, Carvalho NR, Soares FAA, Rocha JBT, Emanuelli T, Bürger ME (2011) Exercise affects memory acquisition, anxiety-like symptoms and activity of membrane bound enzyme in brain of rats fed with different dietary fats: impairments of trans fat. Neuroscience 195:80–88

    Article  CAS  PubMed  Google Scholar 

  • Teixeira AM, Dias VT, Pase CS, Roversi K, Boufleur N, Barcelos RCS, Benvegnú DM, Trevizol F, Dolci GS, Carvalho NR, Quatrin A, Soares FAA, Reckziegel P, Segat HJ, Rocha JBT, Emanuelli T, Bürger ME (2012) Could dietary trans fatty acids induce movement disorders? Effects of exercise and its influence on Na + K+-ATPase and catalase activity in rat striatum. Behav Brain Res 226(2):504–510

    Article  CAS  PubMed  Google Scholar 

  • Teuchert-Noodt G, Dawirs RR, Hildebrandt K (2000) Adult treatment with methamphetamine transiently decreases dentate granule cell proliferation in the gerbil hippocampus. J Neural Transm 107(2):133–143

    Article  CAS  PubMed  Google Scholar 

  • Trevizol F, Benvegnú DM, Barcelos RCS, Boufleur N, Dolci GS, Müller LG, Pase CS, Reckziegel P, Dias VT, Segat H, Teixeira AM, Emanuelli T, Rocha JB, Bürger ME (2011) Comparative study between n-6, trans and n-3 fatty acids on repeated amphetamine exposure: a possible factor for the development of mania. Pharmacol Biochem Behav 97(3):560–565

    Article  CAS  PubMed  Google Scholar 

  • Trevizol F, Roversi K, Dias VT, Kr Roversi, Pase CS, Barcelos RCS, Benvegnú DM, Kuhn FT, Dolci GS, Ross DH, Veit JC, Piccolo J, Emanuelli T, Bürger ME (2013) Influence of lifelong dietary fats on the brain fatty acids and amphetamine-induced behavioral responses in adult rat. Prog Neuropsychopharmacol Biol Psychiatry 45:215–222

    Article  CAS  PubMed  Google Scholar 

  • Trevizol F, Dias VT, Roversi K, Barcelos RCS, Kuhn FT, Kr Roversi, Pase CS, Golombieski R, Veit JC, Piccolo J, Emanuelli T, Rocha JBT, Bürger ME (2014) Cross-generational trans fat intake modifies BDNF mRNA in the hippocampus: impact on memory loss in a mania animal model. Hippocampus 00:1–10

    Google Scholar 

  • Tyagi E, Zhuang Y, Agrawal R, Ying Z, Gomez-Pinilla F (2015) Interactive actions of BDNF methylation and cell metabolism for building neural resilience under the influence of diet. Neurobiol Dis 73:307–318

    Article  CAS  PubMed  Google Scholar 

  • Venkatesan A, Uzasci L, Chen Z, Rajbhandari L, Anderson C, Lee MH, Bianchet MA, Cotter R, Song H, Nath A (2011) Impairment of adult hippocampal neural progenitor proliferation by methamphetamine: role for nitrotyrosination. Mol Brain 4:28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vines A, Delattre AM, Lima MMS, Rodrigues LS, Suchecki D, Machado RB, Tufik S, Pereira SIR, Zanata SM, Ferraz AC (2012) The role of 5-HT1a receptors in fish oil-mediated increased BDNF expression in the rat hippocampus and cortex: a possible antidepressant mechanism. Neuropharmacology 62(1):184–191

    Article  CAS  PubMed  Google Scholar 

  • Wandall B (2008) The controversy over trans fatty acids: effects early in life. Food Chem Toxicol 46(12):3571–3579

    Article  CAS  PubMed  Google Scholar 

  • Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI (2002) The role of polyunsaturated fatty acids in restoring the aging neuronal membrane. Neurobiol Aging 23(5):843–853

    Article  CAS  PubMed  Google Scholar 

  • Yehuda S, Rabinovitz S, Mostofsky DI (2005) Essential fatty acids and the brain: from infancy to aging. Neurobiol Aging 1:98–102

    Article  Google Scholar 

  • Zimmer L, Delpal S, Guilloteau D, Aioun J, Durand G, Chalon S (2000) Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex. Neurosci Lett 284:25–28

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq, Brazil (Edital Universal 2012-475226/2012-7) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul-FAPERGS, RS, Brazil (Edital PRONEM 11/2074-8). Authors are grateful to CAPES (V.T.D; L.T.V.; C.S.P.; K.R.), FAPERGS (F.T.K.) and CNPq (Kr.R.) for the fellowships, as well as to CNPq (T.E.; M.E.B.) for the research grants. The authors are grateful to Herbarium® for their donation of fish oil capsules, as well to Cleopatra da Silva Planeta and Elisabete Zocal Paro Lepera (UNESP) for the opportunity to learn and to participate in technical lessons and practices about surgery.

Author information

Authors and Affiliations

  1. Pharmacology Post Graduation Program, Physiology and Pharmacology Department, Federal University of Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil

    Fábio Teixeira Kuhn, Verônica Tironi Dias, Camila Simonetti Pase, Katiane Roversi, Juliana Cristina Veit, Tatiana Emanuelli & Marilise Escobar Bürger

  2. Programa de Pós-Graduação em Bioquímica Toxicológica, UFSM, Santa Maria, RS, Brazil

    Luciana Taschetto Vey & Marilise Escobar Bürger

  3. Departamento de Fisiologia e Farmacologia, UFSM, Santa Maria, RS, Brazil

    Karine Roversi, Daniele Leão de Freitas & Marilise Escobar Bürger

  4. Departamento de Ciência e Tecnologia dos Alimentos, UFSM, Santa Maria, RS, Brazil

    Tatiana Emanuelli

Authors
  1. Fábio Teixeira Kuhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Verônica Tironi Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karine Roversi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luciana Taschetto Vey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniele Leão de Freitas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Camila Simonetti Pase
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Katiane Roversi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Juliana Cristina Veit
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tatiana Emanuelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marilise Escobar Bürger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marilise Escobar Bürger.

Ethics declarations

Conflict of interest

Authors report no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kuhn, F.T., Dias, V.T., Roversi, K. et al. Cross-Generational trans Fat Consumption Favors Self-Administration of Amphetamine and Changes Molecular Expressions of BDNF, DAT, and D1/D2 Receptors in the Cortex and Hippocampus of Rats. Neurotox Res 28, 319–331 (2015). https://doi.org/10.1007/s12640-015-9549-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-015-9549-5

Keywords

Search

Navigation