Skip to main content
SpringerLink
Log in

Conditioning versus priming of dopaminergic grafts by amphetamine

  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Previous treatment with amphetamine can influence the rotational response induced by amphetamine in rats with dopaminergic grafts. In order to distinguish whether this is due to graft “priming” or conditioning effects of the drug, groups of adult rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra, or with the lesion plus grafts of embryonic mesencephalic tissue in the striatum, were exposed to either: (1) amphetamine in the test environment and saline in the home cage; (2) saline in the test environment and amphetamine in the home cage; or (3) saline in the test environment and saline in the home cage. During this conditioning stage of the experiment, rats with the lesion alone rotated ipsilaterally and rats with the lesion plus grafts contralaterally when tested after administration of amphetamine. The rotation sensitized, i.e. the rats with lesions made more ipsilateral and the rats with grafts more contralateral turns, with repeated injections of the drug. On a subsequent no-drug test, only the rats with grafts which had previously experienced amphetamine in the test environment (1) showed conditioned contralateral rotation. Rats with grafts which had received the same number of amphetamine injections, but experienced the effects of the drug in the home cage (2), rotated ipsilaterally on the no-drug test to the same extent as rats with grafts which had received only saline (3). Thus, amphetamine treatment per se did not “prime” grafts. Rather, the response of the rats with grafts was the result of formation of a conditioned association between the amphetamine and the environment with which it had been paired. Also, there was no evidence for graft “priming” in subsequent tail-pinch and iced water rotation tests. Grafts reduced ipsilateral rotation in these tests, but the reduction was independent of prior treatment with amphetamine.

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

  • Abercrombie M (1946) Estimation of nuclear population from microtome sections. Anat Rec 94:239–247

    Google Scholar 

  • Abrous DN, Torres EM, Annett LE, Reading PJ, Dunnett SB (1992) Intrastriatal dopamine-rich grafts induce a hyperexpression of c-fos protein when challenged with amphetamine. Exp Brain Res 91:181–190

    Google Scholar 

  • Annett LE, Dunnett SB, Martel FL, Rogers DC, Ridley RM, Baker HF, Marsden CD (1990) A functional assessment of embryonic dopaminergic grafts in the marmoset. Prog Brain Res 82:535–542

    Google Scholar 

  • Beninger RJ, Hahn BL (1983) Pimozide blocks establishment but not expression of amphetamine-produced environment specific conditioning. Science 220:1304–1306

    Google Scholar 

  • Björklund A, Stenevi U (1979) Reconstruction of the nigrostriatal dopamine pathway by intracerebral neural transplants. Brain Res 177:555–560

    Google Scholar 

  • Björklund A, Dunnett SB, Stenevi U, Lewis ME, Iversen SD (1980) Reinnervation of the denervated striatum by substantia nigra transplants: functional consequences as revealed by pharmacological and sensorimotor testing. Brain Res 199:307–333

    Google Scholar 

  • Carey RJ (1986) Conditioned rotational behaviour in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. Brain Res 365:379–382

    Google Scholar 

  • Carey RJ (1990) Dopamine receptors mediate drug-induced but not pavlovian conditioned contralateral rotation in the unilateral 6-OHDA animal model. Brain Res 515:292–298

    Google Scholar 

  • Cenci MA, Kalen P, Mandel RJ, Wictorin K, Björklund A (1992) Dopaminergic transplants normalize amphetamine- and apomorphine-induced fos expression in the 6-hydroxydopamine lesioned striatum. Neuroscience 46:943–957

    Google Scholar 

  • Dawson TM, Dawson VL, Gage FH, Fisher LJ, Hunt MA, Wamsley JK (1991) Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantai nigra. Exp Neurol 111:282–292

    Google Scholar 

  • Di Lullo SL, Martin-Iverson MT (1991) Presynaptic dopaminergic neurotransmission mediates amphetamine-induced unconditioned but not amphetamine-conditioned locomotion and defecation in the rat. Brain Res 568:45–54

    Google Scholar 

  • Dunnett SB, Björklund A, Stenevi U, Iversen SD (1981) Behavioural recovery following transplantaion of substantia nigra in rats subjected to unilateral 6-OHDA lesions of the nigrostriatal pathway. I. Unilateral lesions. Brain Res 215:147–161

    Google Scholar 

  • Dunnett SB, Björklund A, Stenevi U, Iversen SD (1983) Intracerebral grafting of neuronal cell suspensions. IV. Behavioural recovery in rats with unilateral implants of nigral cell suspensions in different forebrain sites. Acta Physiol Scand [Suppl] 522:29–37

    Google Scholar 

  • Dunnett SB, Hernandez TD, Summerfield A, Jones GH, Arbuthnott G (1988) Graft-derived recovery from 6-OHDA lesions: specificity of ventral mesencephalic graft tissues. Exp Brain Res 71:411–424

    Google Scholar 

  • Dunnett SB, Whishaw IQ, Rogers DC and Jones GH (1987) Dopamine-rich grafts ameliorate whole body motor asymmetry and sensory neglect but not independent limb use in rats with 6-hydroxydopamine lesions. Brain Res 415:63–78

    Google Scholar 

  • Freed WJ (1991) Substantia nigra grafts and Parkinson's disease: from animal experiments to human therapeutic trials. Rest Neurol Neurosci 3:109–134

    Google Scholar 

  • Freed WJ, Ko GN, Niehoff DL, Kuhar MJ, Hoffer BJ, Olsen L, Cannon-Spoor HE, Morihisa JM, Wyatt RJ (1983) Normalization of spiroperidol binding in the denervated rat striatum by homologous grafts of substantia nigra. Science 222:937–939

    Google Scholar 

  • Gaudin DP, Rioux L, Bedard PJ (1990) Fetal dopamine neuron transplants prevent behavioural supersensitivity induced by repeated administration of 1-dopa in the rat. Brain Res 506:166–168

    Google Scholar 

  • Herman JP, Abrous N, LeMoal M (1991) Anatomical and behavioural comparison of unilateral dopamine-rich grafts implanted into the striatum of neonatal and adult rats. Neuroscience 40:465–475

    Google Scholar 

  • Herman JP, Choulli K, LeMoal M (1985) Hyper-reactivity to amphetamine in rats with dopaminergic grafts. Exp Brain Res 60:521–526

    Google Scholar 

  • Herman JP, Choulli K, Abrous N, LeMoal M (1989) Intracerebral grafts of dopaminergic neurons: a discussion of their functional effects and mechanisms of action. In: Gage F, Privat A, Christen Y (eds) Neuronal grafting and Alzheimer's disease. Springer, Berlin Heidelberg New York, pp 21–33

    Google Scholar 

  • Herman JP, Lupp A, Abrous N, LeMoal M, Hertting G, Jackisch R (1988) Intrastriatal dopaminergic grafts restore inhibitory control over striatal cholinergic neurons. Exp Brain Res 73:236–248

    Google Scholar 

  • Herman JP, Rouge-Pont F, LeMoal M, Abrous DN (1993) Mechanisms of amphetamine-induced rotation in rats with unilateral intrastriatal grafts of embryonic dopaminergic neurons: a pharmacological and biochemical analysis. Neuroscience (in press)

  • Hiroi N, White NM (1989) Conditioned stereotypy: behavioural specification of the UCS and pharmacological investigation on the neural change. Pharmacol Biochem Behav 32:249–258

    Google Scholar 

  • Kelley AE, Domesick VB, Nauta WJH (1982) The amygdalostriatal projection in the rat. An anatomical study by anterograde and retrograde tracing methods. Neuroscience 7:615–630

    Google Scholar 

  • Mandel RJ, Brundin P, Björklund A (1990) The importance of graft placement and task complexity for transplant-induced recovery of simple and complex sensorimotor deficits in dopamine-denervated rats. Eur J Neuroscience 2:888–894

    Google Scholar 

  • Manier M, Abrous DN, Feuerstein C, LeMoal M, Herman JP (1991) Increase of striatal methionine enkephalin content following lesion of the nigrostriatal dopaminergic pathway in adult rats and reversal following the implantation of embryonic dopaminergic neurons: a quantitative immunohistochemical analysis. Neuroscience 42:427–439

    Google Scholar 

  • McGeorge AJ, Faull RLM (1989) The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience 29:503–537

    Google Scholar 

  • Rioux L, Gaudin DP, Bui LK, Gregoire L, DiPaolo T, Bedard PJ (1991) Correlation of functional recovery after a 6-hydroxydopamine lesion with survival of grafted fetal neurons and release of dopamine in the striatum of the rat. Neuroscience 40:123–131

    Google Scholar 

  • Robertson GS, Fine A, Robertson HA (1991) Dopaminergic grafts in the striatum reduce D1 but not D2 receptor-mediated rotation in 6-OHDA-lesioned rats. Brain Res 539:304–311

    Google Scholar 

  • Robinson TE (1984) Behavioural sensitization: characterization of enduring changes in rotation behaviour produced by intermittent injections of amphetamine in male and female rats. Psychopharmacology (Berl) 84:466–475

    Google Scholar 

  • Robinson TE, Becker JB (1986) Enduring changes in brain and behaviour produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res Brain Res Rev 11:157–198

    Google Scholar 

  • Savasta M, Mennicken F, Chritin M, Abrous DN, Feurstein C, LeMoal M, Herman JP (1992) Intrastriatal dopamine-rich implants reverse the changes in dopamine D2 receptor densities caused by 6-hydroxydopamine lesion of the nigrostriatal pathway in rats: an autoradiographic study. Neuroscience 46:729–738

    Google Scholar 

  • Schiff SR (1982) Conditioned dopaminergic activity. Biol Psychiatry 17:135–154

    Google Scholar 

  • Schmidt RH, Björklund A, Stenevi U, Dunnett SB, Gage FH (1983) Intracerebral grafting of neuronal cell suspensions. III. Activity of intrastriatal nigral suspension implants as assessed by measurements of dopamine synthesis and metabolism. Acta Physiol Scand [Suppl] 522:19–28

    Google Scholar 

  • Snyder-Keller AM, Lund RD (1990) Amphetamine sensitization of stress-induced turning in animals given unilateral dopamine transplants in infancy. Brain Res 514:143–146

    Google Scholar 

  • Strecker RE, Sharp T, Brundin P, Zetterström T, Ungerstedt U, Björklund A (1987) Autoregulation of dopamine release and metabolism by intrastriatal nigral grafts as revealed by intracerebral dialysis. Neuroscience 22:169–178

    Google Scholar 

  • Strömberg I, Gerhardt G, van Horne C, Bygdeman M, Olson L, Hoffer B (1991) Electrophysiological and in vivo electrochemical recordings in rats with intraventricular human xenografts. In: Lindvall O, Björklund A, Widner H (eds) Intracerebral transplantation in movement disorders. Elsevier, Amsterdam New York pp 303–311

    Google Scholar 

  • Ungerstedt U and Arbuthnott GW (1970) Quantitative recording of rotational behaviour in rats with 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res 24:485–493

    Article  CAS  PubMed  Google Scholar 

  • Winer BJ (1974) Statistical principles in experimental design, 2nd edn. McGraw Hill, New York

    Google Scholar 

  • Zetterström T, Brundin P, Gage FH, Sharp T, Isacson O, Dunnett SB, Ungerstedt U, Björklund A (1986) In vivo measurement of spontaneous release and metabolism of dopamine from intrastriatal grafts using intracerebral dialysis. Brain Res 362:344–349

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental Psychology, University of Cambridge, Downing Street, CB2 3EB, Cambridge, UK

    L. E. Annett, P. J. Reading, D. Tharumaratnam, D. N. Abrous, E. M. Torres & S. B. Dunnett

Authors
  1. L. E. Annett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. J. Reading
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Tharumaratnam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. N. Abrous
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. M. Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. B. Dunnett
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Annett, L.E., Reading, P.J., Tharumaratnam, D. et al. Conditioning versus priming of dopaminergic grafts by amphetamine. Exp Brain Res 93, 46–54 (1993). https://doi.org/10.1007/BF00227779

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00227779

Key words

Search

Navigation