Skip to main content
SpringerLink
Log in

Striatal output markers do not alter in response to circling behaviour in 6-OHDA lesioned rats produced by acute or chronic administration of the monoamine uptake inhibitor BTS 74 398

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

The monoamine uptake inhibitor BTS 74 398 induces ipsilateral circling in 6-hydroxydopamine (6-OHDA) lesioned rats without induction of abnormal motor behaviours associated with L-dopa administration. We examined whether this was reflected in the expression of peptide mRNA in the direct and indirect striatal output pathways.

6-OHDA lesioning of the nigrostriatal pathway increased striatal expression of PPE-A mRNA and decreased levels of PPT mRNA with PPE-B mRNA expression remaining unchanged. Acute L-dopa administration normalised PPE-A mRNA and elevated PPT mRNA while PPE-B mRNA expression remained unchanged. Acute administration of BTS 74 398 did not alter striatal peptide mRNA levels. Following chronic treatment with L-dopa, PPE-A mRNA expression in the lesioned striatum continued to be normalised and PPT mRNA was increased compared to the intact side. PPE-B mRNA expression was also markedly increased relative to the non-lesioned striatum. Chronic BTS 74 398 administration did not alter mRNA expression in the 6-OHDA lesioned striatum although small increases in PPT mRNA expression in the intact and sham lesioned striatum were observed.

The failure of BTS 74 398 to induce changes in striatal neuropeptide mRNA correlated with its failure to induce abnormal motor behaviours or behavioural sensitisation but does not explain how it produces a reversal of motor deficits. An action in another area of the brain appears likely and may explain the subsequent failure of BTS 74 398 and related compounds to exert anti-parkinsonian actions in man.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • M Andersson A Hilbertson MA Cenci (1999) ArticleTitleStriatal fosB expression is causally linked with L-Dopa-induced abnormal involuntary movements and the associated upregulation of striatal prodynorphin mRNA in a rat model of Parkinson’s disease Neurobiol Dis 6 461–474 Occurrence Handle10600402 Occurrence Handle10.1006/nbdi.1999.0259 Occurrence Handle1:CAS:528:DyaK1MXnvFeku74%3D

    Article  PubMed  CAS  Google Scholar 

  • M Bara-Jiminez T Dimitrova A Sherzai A Favit M Mouradian TN Chase (2004) ArticleTitleEffects of monoamine reuptake inhibitor NS 2330 in advanced Parkinson’s disease Mov Dis 19 1183–1186 Occurrence Handle10.1002/mds.20124

    Article  Google Scholar 

  • K Campbell K Wictorin A Bjorklund (1992) ArticleTitleDifferential regulation of neuropeptide mRNA expression in intrastriatal striatal transplants by host dopaminergic afferents Proc Natl Acad Sci USA 89 10489–10493 Occurrence Handle1438238 Occurrence Handle10.1073/pnas.89.21.10489 Occurrence Handle1:CAS:528:DyaK3sXhs1yjtw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • RJ Carey (1991) ArticleTitleChronic L-dopa treatment in the unilateral 6-OHDA rat: evidence for behavioral sensitization and biochemical tolerance Brain Res 568 205–214 Occurrence Handle1814568 Occurrence Handle10.1016/0006-8993(91)91399-L Occurrence Handle1:CAS:528:DyaK38XpvFWrug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • A Carta S Fenu M Morelli (2001) ArticleTitleAlterations in GAD67, dynorphin and enkephalin mRNA in striatal output neurons following priming in the 6-OHDA model of Parkinson’s disease Neurol Sci 22 59–60 Occurrence Handle11487201 Occurrence Handle10.1007/s100720170046 Occurrence Handle1:STN:280:DC%2BD3MvktVKgsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • MA Cenci CS Lee A Bjorklund (1998) ArticleTitleL-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin- and glutamic acid decarboxylase mRNA Eur J Neurosci 10 2694–2706 Occurrence Handle9767399 Occurrence Handle10.1046/j.1460-9568.1998.00285.x Occurrence Handle1:STN:280:DyaK1M7ksFKrsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • SL Collins PM Kunko B Ladenheim JL Cadet FI Carroll S Izenwasser (2002) ArticleTitleChronic cocaine increases kappa-opioid receptor density: lack of effect by selective dopamine uptake inhibitors Synapse 45 153–158 Occurrence Handle12112394 Occurrence Handle10.1002/syn.10091 Occurrence Handle1:CAS:528:DC%2BD38XmtVegsbk%3D

    Article  PubMed  CAS  Google Scholar 

  • M Dziedzicka-Wasylewska D Dlaboga K Pierzchala-Koziec Z Rogoz (2002) ArticleTitleEffect of tianeptine and fluoxetine on the levels of Met-enkephalin and mRNA encoding proenkephalin in the rat J Physiol Pharmacol 53 117–125 Occurrence Handle11939714 Occurrence Handle1:CAS:528:DC%2BD38Xjt1Wqurk%3D

    PubMed  CAS  Google Scholar 

  • TM Engber Z Susel S Kuo CR Gerfen TN Chase (1991) ArticleTitleLevodopa replacement therapy alters enzyme activities in striatum and neuropeptide content in striatal output regions of 6-hydroxydopamine lesioned rats Brain Res 552 113–118 Occurrence Handle1717109 Occurrence Handle10.1016/0006-8993(91)90667-K Occurrence Handle1:CAS:528:DyaK3MXlt1KrurY%3D

    Article  PubMed  CAS  Google Scholar 

  • F Fornai AB di Poggio A Pellegrini S Ruggieri A Paparelli (2007) ArticleTitleNoradrenaline in Parkinson’s disease: from disease progression to current therapeutics Curr Med Chem 14 2330–2334 Occurrence Handle17896981 Occurrence Handle10.2174/092986707781745550 Occurrence Handle1:CAS:528:DC%2BD2sXhtVKqtrjK

    Article  PubMed  CAS  Google Scholar 

  • EJ Frackiewicz SS Jhee TM Shiovitz J Webster C Topham RC Dockens D Whigan DE Salazaar NR Cutler (2002) ArticleTitleBrasofensine treatment for Parkinson’s disease in combination with levodopa/carbidopa Ann Pharmacother 36 225–230 Occurrence Handle11847938 Occurrence Handle10.1345/aph.1A152 Occurrence Handle1:CAS:528:DC%2BD38XitFOjtLw%3D

    Article  PubMed  CAS  Google Scholar 

  • CR Gerfen WS Young SuffixIII (1988) ArticleTitleDistribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study Brain Res 460 161–167 Occurrence Handle2464402 Occurrence Handle10.1016/0006-8993(88)91217-6 Occurrence Handle1:STN:280:BiaC3MfpsV0%3D

    Article  PubMed  CAS  Google Scholar 

  • CR Gerfen JF McGinty WS Young SuffixIII (1991) ArticleTitleDopamine differentially regulates dynorphin, substance P, and enkephalin expression in striatal neurons: in situ hybridization histochemical analysis J Neurosci 11 1016–1031 Occurrence Handle1707092 Occurrence Handle1:CAS:528:DyaK3MXlvF2hsrw%3D

    PubMed  CAS  Google Scholar 

  • MJ Hansard LA Smith MJ Jackson S Cheetham P Jenner (2002) ArticleTitleDopamine but not norepinephrine of serotonin reuptake inhibition reverses motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates J Pharm Exp Ther 303 952–958 Occurrence Handle10.1124/jpet.102.039743 Occurrence Handle1:CAS:528:DC%2BD38Xptlamt7g%3D

    Article  CAS  Google Scholar 

  • MJ Hansard LA Smith MJ Jackson S Cheetham P Jenner (2004) ArticleTitleThe monoamine reuptake inhibitor BTS 74398 fails to evoke established dyskinesia but does not synergise with levodopa in MPTP-treated primates Mov Disord 19 15–21 Occurrence Handle14743355 Occurrence Handle10.1002/mds.10596

    Article  PubMed  Google Scholar 

  • RA Hauser L Salin N Juhel VL Konyago InstitutionalAuthorNamethe NS 2330 Monotherapy PD Study Group (2007) ArticleTitleRandomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson’s disease Mov Dis 22 359–365 Occurrence Handle10.1002/mds.21258

    Article  Google Scholar 

  • B Henry AR Crossman JM Brotchie (1998) ArticleTitleCharacterization of enhanced behavioral responses to L-DOPA following repeated administration in the 6-hydroxydopamine-lesioned rat model of Parkinson’s disease Exp Neurol 151 334–342 Occurrence Handle9628768 Occurrence Handle10.1006/exnr.1998.6819 Occurrence Handle1:CAS:528:DyaK1cXkt1Kisrs%3D

    Article  PubMed  CAS  Google Scholar 

  • B Henry AR Crossman JM Brotchie (1999) ArticleTitleEffect of repeated L-DOPA, bromocriptine, or lisuride administration on preproenkephalin-A and preproenkephalin-B mRNA levels in the striatum of the 6-hydroxydopamine-lesioned rat Exp Neurol 155 204–220 Occurrence Handle10072296 Occurrence Handle10.1006/exnr.1998.6996 Occurrence Handle1:CAS:528:DyaK1MXhs1Smu7o%3D

    Article  PubMed  CAS  Google Scholar 

  • B Henry S Duty SH Fox AR Crossman JM Brotchie (2003) ArticleTitleIncreased striatal pre-proenkephalin B expression is associated with dyskinesia in Parkinson’s disease Exp Neurol 183 458–468 Occurrence Handle14552886 Occurrence Handle10.1016/S0014-4886(03)00064-5 Occurrence Handle1:CAS:528:DC%2BD3sXnvVyktLs%3D

    Article  PubMed  CAS  Google Scholar 

  • MT Herrero SJ Augood EC Hirsch F Javoy-Agid MR Luquin Y Agid JA Obeso PC Emson (1995) ArticleTitleEffects of L-DOPA on preproenkephalin and preprotachykinin gene expression in the MPTP-treated monkey striatum Neuroscience 68 1189–1198 Occurrence Handle8544992 Occurrence Handle10.1016/0306-4522(95)00120-8 Occurrence Handle1:CAS:528:DyaK2MXotlWhsL0%3D

    Article  PubMed  CAS  Google Scholar 

  • YL Hurd M Herkenham (1992) ArticleTitleInfluence of a single injection of cocaine, amphetamine or GBR 12909 on mRNA expression of striatal neuropeptides Brain Res Mol Brain Res 16 97–104 Occurrence Handle1281257 Occurrence Handle10.1016/0169-328X(92)90198-K Occurrence Handle1:CAS:528:DyaK3sXnsFE%3D

    Article  PubMed  CAS  Google Scholar 

  • J Jolkkonen P Jenner CD Marsden (1995) ArticleTitleL-DOPA reverses altered gene expression of substance P but not enkephalin in the caudate-putamen of common marmosets treated with MPTP Brain Res Mol Brain Res 32 297–307 Occurrence Handle7500841 Occurrence Handle10.1016/0169-328X(95)00084-6 Occurrence Handle1:CAS:528:DyaK2MXns1Gisb0%3D

    Article  PubMed  CAS  Google Scholar 

  • KM Koochesfahani R Fuente-Fernandez V Sossi M Schulzer LN Yatham TJ Ruth S Blinder A Stoessl (2006) ArticleTitleOral methylphenidate fails to elicit significant changes in extracellular putaminal dopamine levels in Parkinson’s disease patients: positrol emission tomographic studies Mov Disord 21 970–975 Occurrence Handle16570297 Occurrence Handle10.1002/mds.20857

    Article  PubMed  Google Scholar 

  • EL Lane SC Cheetham P Jenner (2005) ArticleTitleRepeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6-hydroxydopamine lesioned rat without sensitising motor behaviours Eur J Neurosci 21 179–186 Occurrence Handle15654855 Occurrence Handle10.1111/j.1460-9568.2004.03834.x Occurrence Handle1:STN:280:DC%2BD2M%2FivVCntg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • M Lundblad M Andersson C Winkler D Kirik N Wierup MA Cenci (2002) ArticleTitlePharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson’s disease Eur J Neurosci 15 120–132 Occurrence Handle11860512 Occurrence Handle10.1046/j.0953-816x.2001.01843.x Occurrence Handle1:STN:280:DC%2BD387ktFynug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • A Mura M Mintz J Feldon (2002) ArticleTitleBehavioral and anatomical effects of long-term L-dihydroxyphenylalanine (L-DOPA) administration in rats with unilateral lesions of the nigrostriatal system Exp Neurol 177 252–264 Occurrence Handle12429227 Occurrence Handle10.1006/exnr.2002.7976 Occurrence Handle1:CAS:528:DC%2BD38XosVanurc%3D

    Article  PubMed  CAS  Google Scholar 

  • JA Obeso F Grandas J Vaamonde MR Luquin J Artieda G Lera ME Rodriguez JM Martinez-Lage (1989) ArticleTitleMotor complications associated with chronic levodopa therapy in Parkinson’s disease Neurology 39 11–19 Occurrence Handle2685647 Occurrence Handle1:STN:280:By%2BD28jgs1M%3D

    PubMed  CAS  Google Scholar 

  • G Paxinos C Watson (1987) The rat brain in stereotaxic coordinates Academic Press New York

    Google Scholar 

  • RK Pearce LA Smith MJ Jackson T Banerji J Scheel-Kruger P Jenner (2002) ArticleTitleThe monoamine reuptake blocker brasofensine reverses akinesia without dyskinesia in MPTP-treated and levodopa-primed common marmosets Mov Disord 17 877–886 Occurrence Handle12360536 Occurrence Handle10.1002/mds.10238

    Article  PubMed  Google Scholar 

  • P Ravenscroft S Chalon JM Brotchie AR Crossman (2004) ArticleTitleRopinirole versus L-DOPA effects on striatal opioid peptide precursors in a rodent model of Parkinson’s disease: implications for dyskinesia Exp Neurol 185 36–46 Occurrence Handle14697317 Occurrence Handle10.1016/j.expneurol.2003.09.001 Occurrence Handle1:CAS:528:DC%2BD3sXhtVShsrvE

    Article  PubMed  CAS  Google Scholar 

  • P Romualdi C D’Addario S Ferri BM Cox S Izenwasser (2001) ArticleTitleChronic GBR 12909 administration differentially alters prodynorphin gene expression compared to cocaine Eur J Pharmacol 413 207–212 Occurrence Handle11226394 Occurrence Handle10.1016/S0014-2999(01)00776-2 Occurrence Handle1:CAS:528:DC%2BD3MXhsVOht7w%3D

    Article  PubMed  CAS  Google Scholar 

  • P Salin G Dziewczapolski OS Gershanik A Nieoullon R Raisman-Vozari (1997) ArticleTitleDifferential regional effects of long-term L-DOPA treatment on preproenkephalin and preprotachykinin gene expression in the striatum of 6-hydroxydopamine-lesioned rat Brain Res Mol Brain Res 47 311–321 Occurrence Handle9221930 Occurrence Handle10.1016/S0169-328X(97)00068-5 Occurrence Handle1:CAS:528:DyaK2sXksVCisL8%3D

    Article  PubMed  CAS  Google Scholar 

  • SP Sivam (1996) ArticleTitleDopaminergic regulation of striatonigral tachykinin and dynorphin gene expression: a study with the dopamine uptake inhibitor GBR-12909 Brain Res Mol Brain Res 35 197–210 Occurrence Handle8717356 Occurrence Handle10.1016/0169-328X(95)00216-F Occurrence Handle1:CAS:528:DyaK28XnslWguw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • SP Sivam GR Breese JE Krause TC Napier RA Mueller JS Hong (1987) ArticleTitleNeonatal and adult 6-hydroxydopamine-induced lesions differentially alter tachykinin and enkephalin gene expression J Neurochem 49 1623–1633 Occurrence Handle2889804 Occurrence Handle10.1111/j.1471-4159.1987.tb01036.x Occurrence Handle1:CAS:528:DyaL2sXmt12rtro%3D

    Article  PubMed  CAS  Google Scholar 

  • JA Smith FM Leslie RS Broide SE Loughlin (1993) ArticleTitleLong-term changes in striatal opioid systems after 6-hydroxydopamine lesion of rat substantia nigra Neuroscience 55 935–951 Occurrence Handle8232904 Occurrence Handle10.1016/0306-4522(93)90309-4 Occurrence Handle1:CAS:528:DyaK3sXms1arsr8%3D

    Article  PubMed  CAS  Google Scholar 

  • M St Hilaire E Landry D Levesque C Rouillard (2003) ArticleTitleDenervation and repeated L-DOPA induce a coordinate expression of the transcription factor NGFI-B in striatal projection pathways in hemi-parkinsonian rats Neurobiol Dis 14 98–109 Occurrence Handle13678671 Occurrence Handle10.1016/S0969-9961(03)00081-0 Occurrence Handle1:CAS:528:DC%2BD3sXnt1amt7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • Udo de Haes JI, Maguire RP, Jager PL, Paans AMJ, den Boer JA (2006) Methylphenidate-induced activation of the anterior cingulated but not the striatum: A [15O]H2O PET study in healthy volunteers. Hum Brain Mapp (in press)

  • P Vernier JF Julien P Rataboul O Fourrier C Feuerstein J Mallet (1988) ArticleTitleSimilar time course changes in striatal levels of glutamic acid decarboxylase and proenkephalin mRNA following dopaminergic deafferentation in the rat J Neurochem 51 1375–1380 Occurrence Handle2459307 Occurrence Handle10.1111/j.1471-4159.1988.tb01100.x Occurrence Handle1:CAS:528:DyaL1MXhsVWk

    Article  PubMed  CAS  Google Scholar 

  • P Voorn G Roest HJ Groenewegen (1987) ArticleTitleIncrease of enkephalin and decrease of substance P immunoreactivity in the dorsal and ventral striatum of the rat after midbrain 6-hydroxydopamine lesions Brain Res 412 391–396 Occurrence Handle2440523 Occurrence Handle10.1016/0006-8993(87)91149-8 Occurrence Handle1:CAS:528:DyaL2sXktFyns7w%3D

    Article  PubMed  CAS  Google Scholar 

  • PD Walker LA Riley RP Hart GM Jonakait (1991) ArticleTitleSerotonin regulation of tachykinin biosynthesis in the rat neostriatum Brain Res 546 33–39 Occurrence Handle1713119 Occurrence Handle10.1016/0006-8993(91)91155-T Occurrence Handle1:CAS:528:DyaK3MXisVWitL8%3D

    Article  PubMed  CAS  Google Scholar 

  • BY Zeng J Jolkkonen P Jenner CD Marsden (1995) ArticleTitleChronic L-DOPA treatment differentially regulates gene expression of glutamate decarboxylase, preproenkephalin and preprotachykinin in the striatum of 6-hydroxydopamine-lesioned rat Neuroscience 66 19–28 Occurrence Handle7637869 Occurrence Handle10.1016/0306-4522(94)00574-O Occurrence Handle1:CAS:528:DyaK2MXls1Shsbw%3D

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurodegenerative Disease Research Centre, School of Health and Biomedical Sciences, King’s College, London, UK

    E. L. Lane & P. Jenner

  2. RenaSci Consulting Ltd, BioCity, Nottingham, UK

    S. Cheetham

Authors
  1. E. L. Lane
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Cheetham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Jenner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. L. Lane.

Additional information

Correspondence: Emma L. Lane, Brain Repair Group, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lane, E., Cheetham, S. & Jenner, P. Striatal output markers do not alter in response to circling behaviour in 6-OHDA lesioned rats produced by acute or chronic administration of the monoamine uptake inhibitor BTS 74 398. J Neural Transm 115, 423–429 (2008). https://doi.org/10.1007/s00702-007-0854-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-007-0854-x

Search

Navigation