Skip to main content
SpringerLink
Log in

Differential regional and kinetics effects of piribedil and bromocriptine on dopamine metabolites: a brain microdialysis study in freely moving rats

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

Brain microdialysis coupled to HPLC was applied to freely moving rats to investigate the regional kinetics of piribedil and bromocriptine on the extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in striatum, nucleus accumbens, and frontal cortex. Both D2 agonists (20 mg/kg i.p.) decreased DOPAC and HVA in the three brain regions. The responsiveness of frontal cortex to both compounds was greater than those previously reported with other dopaminergic drugs. Regional and temporal differences were observed under piribedil: DOPAC and HVA levels decreased more in the nucleus accumbens than in striatum or frontal cortex but increased over basal values from the 5th hour in the frontal cortex suggesting a late stimulatory effect of piribedil on dopamine synthesis in this area. Such regional effects differentiate piribedil from most other D2 agonists and could explain some behavioural and therapeutic actions possibly related to involvement of nucleus accumbens or/and frontal cortex.

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 ED, Keefe KA, Di Frischia DS, Zigmond MJ (1989) Differential effect of stress on in vivo dopamine release in striatum, nucleus accumbens and medial prefrontal cortex. J Neurochem 52: 1655–1658

    PubMed  Google Scholar 

  • Aellig WH, Nuesch E (1977) Comparative pharmacokinetics investigated with tritium — labeled ergot alkaloïds after oral and intravenous administration in man. Int J Clin Pharmacol 15: 106–112

    Google Scholar 

  • Bannon MJ, Roth RH (1983) Pharmacology of mesocortical dopamine neurons. Pharmacol Rev 35: 53–68

    PubMed  Google Scholar 

  • Bannon MJ, Michaud RL, Roth RH (1981) Mesocortical dopamine neurons: lack of autoreceptors modulating dopamine synthesis. Mol Pharmacol 19: 270–275

    PubMed  Google Scholar 

  • Bareggi SR, Markey K, Paoletti R (1978) Mechanisms of action of piribedil on noradrenergic neurons in rat brain. Biochem Pharmacol 27: 2803–2805

    PubMed  Google Scholar 

  • Barton AC, Moore KE, Demarest KT (1987) Differential action of bromocriptine on nigrostriatal versus mesolimbic dopaminergic neurons. J Neural Transm 68: 25–39

    PubMed  Google Scholar 

  • Berger B, Thierry AM, Tassin JP, Moyne MA (1976) Dopaminergic innervation of the rat prefrontal cortex: a fluorecence histochemical study. Brain Res 106: 133–145

    PubMed  Google Scholar 

  • Brannan T, Martinez-Tica J, DiRocco A, Yahr MD (1993) Low and high dose bromocriptine have different effects on striatal dopamine release: an in vivo study. J Neural Transm [PD-Sect] 6: 81–87

    Google Scholar 

  • Butterworth RF, Poignant JC, Barbeau A (1975) Apomorphine and piribedil in rats: biochemical and pharmacologie studies. In: Calne DB, Chase TN, Barbeau A (eds) Advances in neurology, vol 9. Raven Press, New York, pp 307–326

    Google Scholar 

  • Carlsson A (1983) Dopamine receptor agonists: past, present and future. Acta Pharm Suecica [Suppl 1]: 11–15

    Google Scholar 

  • Carlsson A, Engel J, Strombom U, Svensson TH, Waldeck B (1974) Suppression by dopamine agonists of the ethanol induced stimulation of locomotor activity and brain dopamine synthesis. Naunyn Schmiedebergs Arch Pharmacol 283: 117–128

    PubMed  Google Scholar 

  • Carter AJ, Müller RE (1991) Pramipexole, a dopamine D2 autoreceptor agonist, decreases the extracellular concentration of dopamine in vivo. Eur J Pharmacol 200: 65–72

    PubMed  Google Scholar 

  • Corrodi H, Farnebo LO, Fuxe K, Hamberger B, Ungerstedt U (1972) ET 495 and brain catecholamine mechanisms. Evidence for stimulation of dopamine receptors. Eur J Pharmacol 20: 195–204

    PubMed  Google Scholar 

  • Costall B, Nailor RJ (1973) The site and mode of action of ET 495 for the mediation of stereotyped behavior in the rat. Naunyn Schmiedebergs Arch Pharmacol 278: 117–133

    PubMed  Google Scholar 

  • Di Chiara G, Porceddu ML, Vargiu L, Stefanini E, Gessa GL (1977) Selective and longlasting stimulation of “regulatory” dopamine receptors by bromocriptine. Naunyn Schmiedebergs Arch Pharmacol 300: 239–245

    PubMed  Google Scholar 

  • Dolphin AC, Jenner P, Sawaya MCB, Marsden CD, Testa B (1977) The effect of bromocriptine on locomotor activity and cerebral catecholamines in rodents. J Pharm Pharmacol 29: 727–734

    PubMed  Google Scholar 

  • Dourish CT (1983) Piribedil: behavioral, neurochemical and clinical profile of a dopamine agonist. Prog Neuropsychopharmacol Biol Psychiatry 7: 3–27

    PubMed  Google Scholar 

  • Dourish CT, Cooper SJ (1982) Suppression of drinking and induction of sedation by a dopamine agonist is blocked by small dose of spiperone. Neuropharmacology 21: 69–72

    PubMed  Google Scholar 

  • Evrard Y (1991) Le piribedil, agoniste dopaminergique. Actualités Thérapeutiques, suppl du JAMA N° hors série (janvier): 16–20

  • Fillenz M, O'Neill RD (1984) Differences in feedback regulation of dopamine release in the striatum and frontal cortex in the rat. J Physiol (London) 349: 11P

  • Fuxe K, Agnati LF, Corrodi H, Eveitt BJ, Hökfelt T, Löfström A, Ungestedt U (1975) Action of dopamine autoreceptor agonists in forebrain and hypothalamus: rotational behavior, ovulation and dopamine turnover. In: Calne DB, Chase TN, Barbeau A (eds) Advances in neurology, vol 9. Raven Press, New York, pp 223–242

    Google Scholar 

  • Fuxe K, Fredholm BB, Ögren SO, Agnati LF, Hökfelt T, Gustaffson JA (1978a) Pharmacological and biochemical evidence for the dopamine agonist effect of bromocriptine. Acta Endocrinol 88: 27–56

    Google Scholar 

  • Fuxe K, Fredholm BB, Ögren SO, Agnati LF, Hökfelt T, Gustaffson JA (1978b) Ergot drugs and central monoaminergic mechanisms: a histochemical, biochemical and behavioral analysis. Fed Proc 37: 2181–2191

    PubMed  Google Scholar 

  • Garattini A, Bareggi SR, Marc V, Calderini G, Morselli PL (1974) Effects of piribedil on noradrenaline and MOPEG-SO4 levels in the rat brain. Eur J Pharmacol 28: 214–216

    PubMed  Google Scholar 

  • Georgieva J, Mohringe B, Magnusson D (1991) The effect of remoxipride on brain dopamine release in freely moving rats: a microdialysis study. In: Rollema H, Westerink BHC, Drijfhout WJ (eds) Monitoring molecules in neuroscience. Proceedings of the 5th International Conference on in vivo methods, Amsterdam, Sept 1991. Krips Repro, Netherlands, pp 337–340

    Google Scholar 

  • Goldstein M, Anagnoste B, Shirron C (1973) The effect of trivastal, haloperidol and dibutyryl cyclic AMP on (14C) dopamine synthesis in rat striatum. J Pharm Pharmacol 25: 348–351

    PubMed  Google Scholar 

  • Gudelsky GA, Moore KE (1976) Differential drug effects on dopamine concentrations and rates of turnover in the median eminence, olfactory tubercle and corpus striatum. J Neural Transm 38: 95–105

    PubMed  Google Scholar 

  • Hall MD, Jenner P, Marsden CD (1983) Differential labelling of dopamine receptors in rat brain in vivo: comparison of3H-piribedil,3H-S 3608 and3H-N,n-propyl-norapomorphine. Eur J Pharmacol 87: 85–94

    PubMed  Google Scholar 

  • Hoffmann IS, Talmaciu RK, Cubeddu LX (1986) Interactions between endogenous dopamine and dopamine agonists at release modulatory receptors: multiple effects of neuronal uptake inhibitors on transmitter release. J Pharmacol Exp Ther 238: 437–446

    PubMed  Google Scholar 

  • Imperato A, Tanda G, Frau R, Di Chiara G (1988) Pharmacological profile of dopamine receptor agonists studied by brain dialysis in behaving rats. J Pharmacol Exp Ther 245: 257–264

    PubMed  Google Scholar 

  • Jackson DM, Martin LP, Larsson LG, Cox RF, Waszczak BL, Ross SB (1990) Behavioural, biochemical and electrophysiological studies on the motor depressant and stimulant effects of bromocriptine. Naunyn Schmiedebergs Arch Pharmacol 342: 290–299

    PubMed  Google Scholar 

  • Julou L, Scatton B, Glowinski J (1977) Acute and chronic treatment with neuroleptics: similarities and differences in their action on nigrostriatal, mesolimbic and mesocortical dopaminergic neurons. In: Costa E, Gessa GL (eds) Adv Biochem Psychopharmacol 17: 617–624

  • Ollat H (1992) Dopaminergic insufficiency reflecting cerebral ageing: value of a dopaminergic agonist, piribedil. J Neurol 239 [Suppl 1]: S13-S16

    PubMed  Google Scholar 

  • Pagliari R, Peyrin L, Cottet-Emard JM, Westerink BHC (1991) In vivo monitoring of noradrenaline release from the frontal cortex of free moving rats using chronic microdialysis and HPLC detection. In: Rollema H, Westerink BHC, Drijfhout WJ (eds) Monitoring molecules in neuroscience. Proceedings of the 5th International Conference on in vivo methods, Amsterdam 1991. Krips Repro, Netherlands, pp 142–145

    Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, New York

    Google Scholar 

  • Ponzio F, Achilli G, Perego C, Algeri S (1981) Differential effects of certain dopaminergic drugs on the striatal concentrations of dopamine metabolites, with special reference to 3-methoxytyramine. Neurosci Lett 27: 61–67

    PubMed  Google Scholar 

  • Radhakishun FS, VanRee JM, Westerink BHC (1988) Scheduled eating increases dopamine release in the nucleus accumbens of food-deprived rats as assessed with online brain dialysis. Neurosci Lett 85: 351–356

    PubMed  Google Scholar 

  • Reiriz J, Mena MA, Bazan E, Muradàs V, Lerma J, Delgado JMR, De Yébenes JG (1989) Temporal profile of levels of monoamines and their metabolites in striata of rats implanted with dialysis tubes. J Neurochem 53: 789–792

    PubMed  Google Scholar 

  • Robinson TE, Camp DM (1991) The feasibility of repeated intracerebral microdialysis for within-subjects design experiments: studies on the mesostriatal system. In: Robinson TE, Justice JB Jr (eds) Microdialysis in the neurosciences. Elsevier, Amsterdam, pp 189–234

    Google Scholar 

  • Rondot P, Bathien N, Ribadeau-Dumas JL (1975) Indications of piribedil in L-dopa treated parkinsonian patients: physiopathological implications. Adv Neuro 9: 373–382

    Google Scholar 

  • Santiago M, Machado A, Cano J (1991) Dopamine release in adult and aged rats: comparison by microdialysis. In: Rollema H, Westerink BHC, Drijfhout WJ (eds) Monitoring molecules in neuroscience. Proceedings of the 5th International Conference on in vivo methods, Amsterdam 1991. Krips Repro, Netherlands, pp 224–226

    Google Scholar 

  • Sarati S, Guiso G, Garattini S, Caccia S (1991) Kinetics of piribedil and effects on dopamine metabolism: hepatic biotransformation is not a determinant of its dopaminergic action in rats. Psychopharmacology 105: 541–545

    PubMed  Google Scholar 

  • Scatton B, Thierry AM, Glowinski J, Julou L (1975) Effect of thiopiperazine and apomorphine on dopamine synthesis in the mesocortical dopaminergic systems. Brain Res 88: 389–393

    PubMed  Google Scholar 

  • Schmitt H, Laubie M, Poignant JC, Krikorian A, Evrard Y, Freyria JL, Arnaud F (1978) Nouvelles indications thérapeutiques d'un agent agoniste dopaminergique: le piribédil. La Semaine des Hôpitaux de Paris 54: 325–334

    Google Scholar 

  • Sharp T, Zetterström T, Ungerstedt U (1986) An in vivo study of dopamine release and metabolism in rat brain regions using intracerebral dialysis. J Neurochem 47: 113–122

    PubMed  Google Scholar 

  • Siegel S, Castellan NJ (1988) Comparison of groups or conditions with a control following the Friedman two-way analysis of variance by ranks. In: Siegel S, Castellan NJ (eds) Non parametric statistics. Mac Graw-Hill, New York, pp 174–184

    Google Scholar 

  • Simon H (1981) Neurones dopaminergiques A10 et système frontal. J Physiol (Paris) 77: 81–95

    Google Scholar 

  • Snider SR, Hutt C, Stein B, Prasad ALN, Fahn S (1976) Correlation of behaviour inhibition or excitation with changes in brain catecholamine turnover. J Pharm Pharmacol 28: 563–566

    PubMed  Google Scholar 

  • Thierry AM, Stinus L, Blanc G, Glowinski J (1973) Some evidence for the existence of dopaminergic neurons in the rat cortex. Brain Res 50: 230–234

    PubMed  Google Scholar 

  • Timmermann W, De Vries JB, Westerink BHC (1990) Effects of D2 agonists on the release of dopamine: localization of the mechanism of action. Naunyn Schmiedebergs Arch Pharmacol 342: 650–654

    PubMed  Google Scholar 

  • Tissari AH, Rossetti ZL, Meloni M, Frau MI, Gessa GL (1983) Autoreceptors mediate the inhibition of dopamine synthesis by bromocriptine and lisuride in rats. Eur J Pharmacol 91: 463–468

    PubMed  Google Scholar 

  • Vahabzadeh A, Fillenz M (1991) Studies on the origin of hippocampal DOPAC using microdialysis. In: Rollema H, Westerink BHC, Drijfhout WJ (eds) Monitoring molecules in neuroscience. Proceedings of the 5th International Conference on in vivo methods, Amsterdam 1991. Krips Repro, Netherlands, pp 345–346

    Google Scholar 

  • Westerink BHC, Justice JR (1991) Microdialysis compared with other in vivo release models. In: Robinson TE, Justice JB Jr (eds) Microdialysis in the neurosciences. Elsevier, Amsterdam, pp 23–41

    Google Scholar 

  • Westerink BHC, Tuntler J, Damsma G, Rollema H, De Vries JB (1987) The use of tetrodotoxin for the characterization of drug-enhanced dopamine release in conscious rats studied by brain dialysis. Arch Pharmacol 336: 502–507

    Google Scholar 

  • Westfall TC, Naes L, Paul C (1983) Relative potency of dopamine agonists on autoreceptor function in various brain regions of the rat. J Pharmacol Exp Ther 224: 199–205

    PubMed  Google Scholar 

  • White FJ, Wang RY (1984) A10 dopaminergic neurons: role of autoreceptors in determining firing rate and sensitivity to dopamine agonists. Life Sci 34: 1161–1170

    PubMed  Google Scholar 

  • Zetterström T, Sharp T, Ungerstedt U (1986) Effect of dopamine D1 and D2 receptor selective drugs on dopamine release and metabolism in rat striatum in vivo. Naunyn Schmiedebergs Arch Pharmacol 334: 117–124

    PubMed  Google Scholar 

  • Zetterström T, Sharp T, Collin AK, Ungerstedt U (1988) In vivo measurement of extracellular dopamine and DOPAC in rat striatum after various dopamine-releasing drugs; implications for the origin of extracellular DOPAC. Eur J Pharmacol 148: 327–334

    PubMed  Google Scholar 

  • Ziegler M, Udo N, Bathien N, Rondot P (1987) Effets immédiats du piribedil sur le tremblement de repos. Precepta medica 2: 56–59

    Google Scholar 

Download references

Author information

Author notes

  1. R. Pagliari

    Present address: Laboratoire de Physiologie, Faculté de Médecine, Lyon

Authors and Affiliations

  1. Laboratoire de Physiologie, Faculté de Médecine, Lyon

    L. Peyrin

  2. IRIS, Courbevoie, France

    O. Crambes

Authors
  1. R. Pagliari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Peyrin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. Crambes
    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

Pagliari, R., Peyrin, L. & Crambes, O. Differential regional and kinetics effects of piribedil and bromocriptine on dopamine metabolites: a brain microdialysis study in freely moving rats. J. Neural Transmission 101, 13–26 (1995). https://doi.org/10.1007/BF01271542

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01271542

Keywords

Search

Navigation