Abstract
The spontaneous motor activity, overt behavioral responses, and concentration of NA and DA in the brain were studied in young rats at different postnatal ages following the administration of l-DOPA (100 mg/kg) or NA and DA receptor-stimulating or blocking agents. l-DOPA induced marked hyperactivity even at one day of age and the duration of the l-DOPA-induced hyperactivity and increase in NA and DA concentrations in the brain decreased with ontogenic development. At 21 days, the apparent behavioral response to l-DOPA was one of depression rather than marked excitation. Pretreatment of 21 day-old animals with MK-486, a peripheral decarboxylase inhibitor, produced excitation with aggressive responses, whereas in younger animals the effect of this drug was only to lengthen the duration of the response. It was concluded that not until around 21 days of age does the capacity of the peripheral decarboxylase become a major factor in determining the behavioral response to l-DOPA.
Clonidine, a NA-receptor-stimulating agent elicited behavioral rssponses from one day of age similar to the responses observed after l-DOPA. A response to apomorphine, a DA-receptor-stimulating agent, was not readily observed until 4 days of age and then the response was rather variable. Marked stereotyped behavior was not observed in response to apomorphine until 21 days of age. This difference between clonidine and apomorphine stimulation was considered to suggest that NA receptors may develop at an earlier age than DA receptors.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agrawal, H. C., Himwich, W. A.: Amino acids, proteins, and monoamines of developing brain. In: Developmental neurobiology, pp. 287–310. W. A. Himwich, ed. Springfield, Ill.: Ch. C. Thomas 1970.
Andén, N. E.: Pharmacological and anatomical implications of induced abnormal movements with DOPA. In: l-DOPA and parkinsonism, pp. 132–143. A. Barbeau and F. H. McDowell, eds. Philadelphia: F. A. Davis Co. 1970.
—, Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol. 11, 303–314 (1970b).
—, Corrodi, H., Fuxe, K., Hökfelt, B., Hökfelt, T., Rydin, C., Svensson, T.: Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci. 9, 513–523 (1970a).
—, Dahlström, A., Fuxe, K., Larsson, K., Olson, L., Ungerstedt, U.: Ascending monoamine neurones to the telencephalon and diencephalon. Acta physiol. scand. 67, 313–326 (1966).
—, Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967).
Bertler, Å.: Occurrence and localization of catecholamines in the human brain. Acta physiol. scand. 51, 97–107 (1961).
—, Carlsson, A., Rosengren, E.: A method for the fluorometric determination of adrenaline and noradrenaline in tissues. Acta physiol. scand. 44, 273–292 (1958).
—, Rosengren, E.: On the distribution in brain of monoamines and of enzymes responsible for their formation. Experientia (Basel) 15, 382 (1959).
Bojanek, J., Bozkowa, K., Kurzepa, A.: The 5-HTP decarboxylase and MAO activities and 5-HT level in subcellular fractions of the liver during development. Biol. Neonat. (Basel) 9, 203–214 (1965/1966).
Carlsson, A.: Biochemical implications of DOPA-induced actions on the central nervous system, with particular reference to abnormal movements. In: l-DOPA and Parkinsonism, pp. 205–213. A. Barbeau and F. H. McDowell, eds. Philadelphia: F. A. Davis Co. 1970.
—, Lindqvist, M.: In Vivo decarboxylation of α-methyl DOPA and α-methyl metatyrosine. Acta physiol. scand. 54, 87–94 (1962).
—, Waldeck, B.: A fluorometric method for the determination of dopamine (3-hydroxytyramine). Acta physiol. scand. 44, 293–298 (1958).
Connor, J. D., Neff, N. H.: Dopamine concentrations in the caudate nucleus of the developing cat. Life Sci. 9, Part 1, 1165–1168 (1970).
Hornykiewicz, O.: Dopamine (3-hydroxytyramine) and brain function. Pharmacol. Rev. 18, 915–964 (1966).
Kellogg, C., Lundborg, P.: Production of (3H) catecholamines in the brain following the peripheral administration of (3H) DOPA during pre- and postnatal development. Brain Res. (in Press) (1971a).
- - Uptake and utilization of (3H) 5-hydroxytryptophan by brain tissue during development. J. Neuropharmacol. (In press) (1971b).
Loizou, L. A.: The development of monoamine-containing neurones in the brain of the albino rat. J. Anat. (Lond.) 104, 588 (1969).
Morpurgo, C.: Aggressive behavior induced by large doses of 2-(2,6-dichlorphenyl ammo)-2-imidazoline hydrochloride (ST 155) in mice. Europ. J. Pharmacol. 3, 374–377 (1968).
Porter, C. C., Watson, L. S., Titus, D. G., Totary, J. A., Byers, S. S.: Inhibition of DOPA decarboxylase by the hydrazine analogue of α-methyl DOPA. Biochem. Pharmacol. 11, 1067–1077 (1962).
Roos, B. E.: Decrease in homovanillic acid as evidence for dopamine receptor stimulation by apomorphine in the neostriatum of the rat. J. Pharm. Pharmacol. 21, 263–264 (1969).
Smith, S. E., Stacey, R. S., Young, I. M.: 5-hydroxytryptamine and 5-hydroxytryptophan decarboxylase activity in the developing nervous system of rats and guinea pigs. In: Pharmacological analysis of central nervous action, pp. 101–105. W. D. M. Paton and P. Lindgren, eds. Oxford: Pergamon Press 1962.
Strömberg, U.: DOPA effects on motility in mice; potentiation by MK 485 and dexchlorpheniramine. Psychopharmacologia (Berl.) 18, 58–67 (1970).
—, Svensson, T.: l-DOPA induced effects on motor activity in mice after inhibition of dopamine-β-hydroxylase. Psychopharmacologia (Berl.) 19, 53–60 (1970).
Svensson, T., Thieme, G.: An investigation of a new instrument to measure motor activity of small animals. Psychopharmacologia (Berl.) 14, 157–163 (1969).
Svensson, T. H., Waldeck, B.: On the role of brain catecholamines in motor activity: experiments with inhibitors of synthesis and of monoamine oxidase. Psychopharmacologia (Berl.) 18, 357–365 (1970).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kellogg, C., Lundborg, P. Ontogenic variations in responses to l-DOPA and monoamine receptor-stimulating agents. Psychopharmacologia 23, 187–200 (1972). https://doi.org/10.1007/BF00401194
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00401194