Skip to main content
Log in

Effects of chronic administration of fenproporex on cognitive and non-cognitive behaviors

Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Fenproporex (Fen) is an amphetamine-based anorectic; amphetamine use causes a broad range of severe cognitive deficits and anxiogenic-like effects. In this study we evaluated pharmacological effects of the chronic administration of Fen on cognitive and non-cognitive behaviors. Male adult Wistar rats received intraperitoneal administration of vehicle (control group) or Fen (6.25, 12.5 or 25 mg/kg) for 14 days; the animals were then subjected to habituation and object recognition tasks in open-field apparatus, and elevated plus-maze task. The administration of Fen (12.5 and 25 mg/kg) impaired habituation during the second exposure to the habituation task. In addition, the same doses of Fen also impaired the performance in object recognition task. In elevated plus-maze task, the administration of Fen (in all doses tested) induced anxiogenic-like effects in rats. Our results suggest that chronic Fen administration alters memory and induces anxiogenic-like effects in rats.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  • Barr JL, Renner KJ, Forster GL (2010) Withdrawal from chronic amphetamine produces persistent anxiety-like behavior but temporally-limited reductions in monoamines and neurogenesis in the adult rat dentate gyrus. Neuropharmacology 59:395–405

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Barr JL, Scholl JL, Solanki RR, Watt MJ, Lowry CA, Renner KJ, Forster GL (2012) Influence of chronic amphetamine treatment and acute withdrawal on serotonin synthesis and clearance mechanisms in the rat ventral hippocampus. Eur J Neurosci 37:479–790

    Article  PubMed Central  PubMed  Google Scholar 

  • Belcher AM, O’Dell SJ, Marshall JF (2005) Impaired objectrecognition memory following methamphetamine, but not p-chloroamphetamine- or d-amphetamine-induced neurotoxicity. Neuropsychopharmacology 30:2026–34

    Article  CAS  PubMed  Google Scholar 

  • Cody JT, Valtier S, Stillman S (1999) Amphetamine and fenproporex levels following multidose administration of fenproporex. J Anal Toxicol 23:187–94

    Article  CAS  PubMed  Google Scholar 

  • Cohen PA (2009) Imported fenproporex-based diet pills from Brazil: a report of two cases. J Gen Intern Med 24:430–33

    Article  PubMed Central  PubMed  Google Scholar 

  • Colman E (2005) Anorectics on trial: a half century of Federal regulation of prescription appetite suppressants. Ann Intern Med 143:380–5

    Article  PubMed  Google Scholar 

  • Comiran E, Souza DZ, Boehl PO, CássiaMariottiKd PF, Duarte Pdo C, De Boni RB, Fröehlich PE, Limberger RP (2012) Fenproporex and amphetamine pharmacokinetics in oral fluid after controlled oral administration of fenproporex. Ther Drug Monit 34:545–53

    Article  CAS  PubMed  Google Scholar 

  • Conway KP, Compton W, Stinson FS, Grant BF (2006) Lifetime comorbidity of DSM-IV mood andanxiety disorders and specific drug use disorders: results from the national epidemiologic surveyon alcohol and related conditions. J Clin Psychiatry 67:247–57

    Article  CAS  PubMed  Google Scholar 

  • Coutts RT, Nazarali AJ, Baker GB, Pasutto FM (1986) Metabolism and disposition of N-(2-cyanoethyl)-amphetamine (fenproporex) and amphetamine: study in the rat brain. Can J Physiol Pharmacol 64:724–8

    Article  CAS  PubMed  Google Scholar 

  • Cruickshank CC, Dyer KR (2009) A review of the clinical pharmacology of methamphetamine. Addiction 104:1085–99

    Article  PubMed  Google Scholar 

  • Gonzalez R, Bechara A, Martin EM (2007) Executive functions among individuals with methamphetamine or alcohol as drugs of choice: preliminary observations. J Clin Exp Neuropsychol 29:155–9

    Article  PubMed  Google Scholar 

  • Graeff FG, Guimaraes FS, De Andrade TG, Deakin JF (1996) Roleof 5-HT in stress, anxiety, and depression. Pharmacol Biochem Behav 54:129–41

    Article  CAS  PubMed  Google Scholar 

  • Guimaraes F, Del Bel EA, Padovan CM, Netto SM, de Almeida RT (1993) Hippocampal 5-HT receptors and consolidation of stressfulmemories. Behav Brain Res 58:133–9

    Article  CAS  PubMed  Google Scholar 

  • Hoffman WF, Moore M, Templin R, McFarland B, Hitzemann RJ, Mitchell SH (2006) Neuropsychological function and delay discounting in methamphetamine-dependent individuals. Psychopharmacol (Berl) 188:162–70

    Article  CAS  Google Scholar 

  • Hogg S (1996) A review of the validity and variability of the elevated plus-maze as an animal model ofanxiety. Pharmacol Biochem Behav 54:21–30

    Article  CAS  PubMed  Google Scholar 

  • Izquierdo I, Medina JH (1997) Memory formation: the sequence of biochemical events in the hippocampus and its connection to activity in other brain structures. Neurobiol Learn Mem 68:285–316

    Article  CAS  PubMed  Google Scholar 

  • Joca SR, Padovan CM, Guimaraes FS (2003) Activation of post-synaptic 5-HT(1A) receptors in the dorsal hippocampus prevents learned helplessness development. Brain Res 978:177–84

    Article  CAS  PubMed  Google Scholar 

  • Kalechstein AD, Newton TF, Green M (2003) Methamphetamine dependence is associated with neurocognitive impairment in the initial phases of abstinence. J Neuropsychiatry Clin Neurosci 15:215–20

    Article  CAS  PubMed  Google Scholar 

  • Mariotti KC, Rossato LG, Fröehlich PE, Limberger RP (2013) Amphetamine-type medicines: a review of pharmacokinetics, pharmacodynamics, and toxicological aspects. Curr Clin Pharmacol 8:350–7

    Article  CAS  PubMed  Google Scholar 

  • Marshall JF, Belcher AM, Feinstein EM, O’Dell SJ (2007) Methamphetamine-induced neural and cognitive changes in rodents. Addiction 102:61–9

    Article  PubMed  Google Scholar 

  • Mattei R, Carlini EA (1996) Acomparative study of the anorectic and behavioral effects of fenproporex on male and female rats. Braz J Med Biol Res 29:1025–30

    CAS  PubMed  Google Scholar 

  • Melo P, Magalhães A, Alves CJ, Tavares MA, de Sousa L, Summavielle T, Moradas-Ferreira P (2012) Methamphetamine mimics the neurochemical profile of aging in rats and impairs recognition memory. Neurotoxicology 33:491–9

    Article  CAS  PubMed  Google Scholar 

  • Nagai T, Takuma K, Dohniwa M, Ibi D, Mizoguchi H, Kamei H, Nabeshima T, Yamada K (2007) Repeated methamphetamine treatment impairs spatial working memory in rats: reversal by clozapine but not haloperidol. Psychopharmacol (Berl) 194:21–32

    Article  CAS  Google Scholar 

  • Nesse RM, Berridge KC (1997) Psychoactive drug use in evolutionary perspective. Science 278:63–6

    Article  CAS  PubMed  Google Scholar 

  • Pélissier-alicot AL, Piercecchi-marti MD, Bartoli C, Kuhlmann E, Coiffait PE, Sanvoisin A, Giocanti D, Léonetti G (2006) Abusive prescription of psychostimulants: a study of two cases. J Forensic Sci 51:407–10

    Article  PubMed  Google Scholar 

  • Pelloux Y, Costentin J, Duterte-Boucher D (2009) Anxiety increases the place conditioning induced by cocaine in rats. Behav Brain Res 197:311–6

    Article  CAS  PubMed  Google Scholar 

  • Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closedarm entries in an elevated plus-maze as a measure of anxiety inthe rat. J Neurosci Methods 14:149–67

    Article  CAS  PubMed  Google Scholar 

  • Reichel CM, Ramsey LA, Schwendt M, McGinty JF, See RE (2012) Methamphetamine-induced changes in the object recognition memory circuit. Neuropharmacology 62:1119–26

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rendell PG, Mazur M, Henry JD (2009) Prospective memory impairment in former users of methamphetamine. Psychopharmacol (Berl) 203:609–16

    Article  CAS  Google Scholar 

  • Rezin GT, Scaini G, Ferreira GK, Cardoso MR, Gonçalves CL, Constantino LS, Deroza PF, Ghedim FV, Valvassori SS, Resende WR, Quevedo J, Zugno AI, Streck EL (2012) Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex. Metab Brain Dis 27:453–8

    Article  CAS  PubMed  Google Scholar 

  • Schroder N, O’Dell SJ, Marshall JF (2003) Neurotoxic methamphetamine regimen severely impairs recognition memory in rats. Synapse 49:89–96

    Article  PubMed  Google Scholar 

  • Simon SL, Domier CP, Sim T, Richardson K, Rawson RA, Ling W (2002) Cognitive performance of current methamphetamine and cocaine abusers. J Addict Dis 21:61–74

    Article  PubMed  Google Scholar 

  • Simon SL, Dacey J, Glynn S, Rawson R, Ling W (2004) The effect of relapse on cognition in abstinent methamphetamine abusers. J Subst Abuse Treat 27:59–66

    Article  PubMed  Google Scholar 

  • Storey JD, Robertson DA, Beattie JE, Reid IC, Mitchell SN, Balfour DJK (2006) Behavioural & neurochemical responses evoked byrepeated exposure to an elevated open platform. Behav Brain Res 166:220–9

    Article  CAS  PubMed  Google Scholar 

  • Vianna MR, Alonso M, Violo H, Quevedo J, De-Paris F, Furman M, de Stein ML, Medina JH, Izquierdo I (2000) Role of hippocampal signaling pathways in long-term memory formation of nonassociative learning task in the rat. Learn Mem 7:333–40

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vianna MR, Izquierdo LA, Barros DM, de Souza MM, Rodrigues C, Sant’Anna MK, Medina JH, Izquierdo I (2001) Pharmacological differences between memory consolidation of habituation to an open field and inhibitory avoidance learning. Braz J Med Biol Res 34:233–40

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by grants from Programa de Pós-graduação em Ciências da Saúde—Universidade do Extremo Sul Catarinense (UNESC), Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina NENASC project, Conselho Nacional de Desenvolvimento Científico e Tecnológico (PRONEX - FAPESC/CNPq), and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Emilio L. Streck.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gonçalves, C.L., Furlanetto, C.B., Valvassori, S.S. et al. Effects of chronic administration of fenproporex on cognitive and non-cognitive behaviors. Metab Brain Dis 30, 583–588 (2015). https://doi.org/10.1007/s11011-014-9617-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-014-9617-1

Keywords

Navigation