Ontogenesis of neostriatal cholinergic neurones in the rat and development of their sensitivity to neuroleptic drugs

  • P. G. Guyenet
  • J. C. Beaujouan
  • J. Glowinski
Short Communication


Simultaneous determinations of the striatal contents in acetylcholine (ACh), choline acetyl-transferase (ChAc) and acetyl-cholinesterase (AChE) were made in neonate rats from day 4 to day 16 after birth. While, during this period, ChAc and AChE increased 14 and 5-fold, respectively, the change of ACh levels was smaller and more gradual. ACh levels were unaltered following the injection of thioproperazine (5 mg/kg) until day 8, then within 6 days the cholinergic neurones developed a full sensitivity to this drug. The sensitivity to haloperidol (4 mg/kg), pimozide (4 mg/kg) and to the dopamine receptor stimulating drug apomorphine (10 mg/kg) appeared along with that to thioproperazine. These data confirm and extend previous reports that rat striatal cholinergic neurones are immature at birth; they suggest, in addition, that the development of dopamine receptors occurs prior to the appearance of functional cholinergic synapses or concomitant with this event.

Key words

Neostriatum Development ACh Dopamine Receptors 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abdel-Latif, A. A., Smith, J. P., Ellington, E. P.: Subcellular distribution of sodium-potassium activated adenosine triphosphatase, acetylcholine and acetylcholinesterase in developing rat brain. Brain Res. 18, 441–450 (1970)Google Scholar
  2. Agid, Y., Guyenet, P., Glowinski, J., Beaujouan, J. C.,Javoy, F.: Inhibitory influence of the nigroneostriatal dopaminergic system on the striatal cholinergic neurons in the rat. Brain Res. 86, 488–492 (1975)Google Scholar
  3. Bartholini, G., Stadler, H., Lloyd, K. G.: The effect of drugs on the release of striatal neurotransmitters. In: Pharmacology and Biochemistry of nigro neostriatal system. CINP Congress, Paris July 1974Google Scholar
  4. Bunney, B. S., Walters, J. R., Roth, R. H., Aghajanian, G. K.: Dopaminergic neurons: effect of antipsychotic drugs and amphetamine on single cell activity. J. Pharmacol. exp. Ther. 185, 560–571 (1973)Google Scholar
  5. Corrodi, H., Fuxe, K., Lidbrink, P.: Interaction between cholinergic and catecholaminergic neurons in rat brain. Brain Res. 43, 397–416 (1972)Google Scholar
  6. Consolo, S., Ladinsky, H., Garrattini, S.: Effect of several dopaminergic drugs and trihexyphenidyl on cholinergic parameters in the rat striatum. J. Pharm. Pharmacol. 26, 275–277 (1974)Google Scholar
  7. Crossland, J.: The use of liquid air in the extraction of ACh. J. Physiol. (Lond.) 114, 318–328 (1951)Google Scholar
  8. Ellman, G. L., Courtney, K. D., Andres, V., Featherstone, R. M.: A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7, 88–95 (1961)Google Scholar
  9. Fonnum, F.: Radiochemical microassays for the determination of choline acetyltransferase and acetylcholinesterase activities. Biochem. J. 115, 465–472 (1969)Google Scholar
  10. Guyenet, P. G., Agid, Y., Javoy, F., Beaujouan, J. C., Glowinski, J.: Action sélective des neuroleptiques sur les neurones cholinergiques du neostriatum chez le rat. C. R. Acad. Sci. (Paris) 278, D, 2679–2682 (1974)Google Scholar
  11. Guyenet, P. G., Agid, Y., Javoy, F., Beaujouan, J.C., Rossier, J., Glowinski, J.: Effects of dopaminergic receptor agonists and antagonists on the activity of the neostriatal cholinergic system. Brain Res. 84, 227–244 (1975)Google Scholar
  12. Hamburgh, M., Flexner, L. B.: Biochemical and physiological differentiation during morphogenesis. XXI. Effect of hypothyroidism and hormone therapy on enzyme activities of the developing cerebral cortex of the rat. J. Neurochem. 1, 279–288 (1957)Google Scholar
  13. Kebabian, J. W., Petzold, G. L., Greengard, P.: Dopamine sensitive adenylate cyclase in caudate nucleus of rat brain and its similarity to the “dopamine receptors”. Proc. nat. Acad. Sci. (Wash.) 69, 2145–2149 (1972)Google Scholar
  14. Keller, H. H., Bartholini, G., Pletscher, A.: Spontaneous and drug induced changes of cerebral dopamine turnover during postnatal development of rats. Brain Res. 64, 371–378 (1973)Google Scholar
  15. Ladinsky, H., Consolo, S., Peri, G., Garattini, S.: Acetylcholine, choline and choline acetyltransferase activity in the developing brain of normal and hypothyroid rats. J. Neurochem. 19, 1947–1952 (1972)Google Scholar
  16. Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the folin phenol reagent. J. biol. Chem. 193, 265–275 (1951)Google Scholar
  17. McGeer, E. G., Fibiger, H. C., Wickson, V.: Differential development of caudate enzymes in the neonatal rat. Brain Res. 32, 433–440 (1971)Google Scholar
  18. Trabucchi, M., Cheney, D., Racagni, G., Costa, E.: Involvement of brain cholinergic mechanisms in the action of chlorpromazine. Nature (Lond.) 249, 664–666 (1974)Google Scholar
  19. Von Hungen, K., Roberts, S., Hill, D. F.: Developmental and regional variations in neurotransmitter-sensitive adenylate cyclase systems in cell-free preparations from rat brain. J. Neurochem. 22, 811–819 (1974)Google Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • P. G. Guyenet
    • 1
  • J. C. Beaujouan
    • 1
  • J. Glowinski
    • 1
  1. 1.Groupe NB (INSERM U. 114)Collège de FranceParisFrance

Personalised recommendations