Skip to main content
SpringerLink
Log in

Influence of 6-hydroxydopamine on the behavioral effects induced by apomorphine or clonidine in rats

  • Animal Studies
  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The aim of this paper is to examine if central chemical sympathectomy induced by two injections of 6-hydroxydopamine (6-OHDA) in a dose of 250 μg intracerebroventricularly (k.c.v.) affects behavioral phenomena elicited by apomorphine (AP) (1 or 1.2 mg/kg i.p.) or clonidine (CL) (0.1 mg/kg, 5 or 1 μg/kg i.p.).

Experiments were carried out on male Wistar rats. The time of duration of several components of behavior and the degree of irritability of rats were measured. Moreover, open field and hole test were performed. The lower dose of AP did not affected behavior of rats. The higher dose increased the locomotor and exploratory activity of animals. 6-OHDA potentiated these effects of AP. CL (0.1 mg/kg) had a depressive effect on the rats' behavior, which was potentiated by 6-OHDA. CL (5 μg/kg) had no effect on the rats' behavior, but in a dose of 1 μg/kg caused excitatory behavior. This type of behavior was abolished by 6-OHDA. In conclusion, central chemical sympathectomy caused increased sensitivity of the central nervous system on AP. Excitatory behavioral effects of CL in low dosage may be connected with stimulation of central adrenergic receptors. Depressive behavioral effect of CL in high dosage is unspecific. Central chemical sympathectomy affects by different methods the reactivity of dopaminergic and noradrenergic neurons.

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

  • Andén, N.-E., Corrodi, H., Fuxe, K., Hökfelt, B., Hökfelt, T., Rydin, C., Svensson, T.: Evidence for a central noradrenaline receptor. Stimulation by clonidine. Life Sci., part I,9, 513–523 (1970)

    Google Scholar 

  • Andén, N.-E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol.19, 627–628 (1967)

    Google Scholar 

  • Andén, N.-E., Strömbom, U., Svensson, T. H.: Dopamine and noradrenaline receptor stimulation: Reversal of reserpine-induced suppression of motor activity. Psychopharmacologia (Berl.)29, 289–298 (1973)

    Google Scholar 

  • Atack, C. V.: The determination of dopamine by a modification of the dihydroxyindole fluorimetric assay. Brit. J. Pharmacol48, 699–714 (1973)

    Google Scholar 

  • Barnett, A., Fiore, J. W.: Hypotensive effects of apomorphine in anaesthetised cats. Europ. J. Pharmacol14, 206–208 (1971)

    Google Scholar 

  • Bartholini, G., Richards, J. G., Pletscher, A.: Dissociation between biochemical and ultrastructural effects of 6-hydroxydopamine in rat brain. Experientia (Basel)26, 142–144 (1970)

    Google Scholar 

  • Bloom, F. E., Algeri, S., Gropetti, A., Revuelta, A., Costa, E.: Lesions of central norepinephrine terminals with 6-OH-dopamine: Biochemistry and fine structure. Science166, 1284–1286 (1969)

    Google Scholar 

  • Brus, R., Herman, Z. S., Kostman, F.: Behavioral effects of norepinephrine and dibutyryl 3′,5′ AMP in centrally sympathectomized rats. Pharmacol. Biochem. Behav.2, 719–724 (1974)

    Google Scholar 

  • Burkard, W. P., Jalfre, M., Blum, J.: Effect of 6-hydroxydopamine on behavior and cerebral amine content in rats. Experientia (Basel)25, 1295–1296 (1969)

    Google Scholar 

  • Costall, B., Naylor, R. J.: On the mode of action of apomorphine. Europ. J. Pharmacol.21, 350–361 (1973)

    Google Scholar 

  • Crossland, J., Slater, P.: The effect of some drugs on the “free” and “bound” acetylcholine content of rat brain. Brit. J. Pharmacol.33, 42–47 (1968)

    Google Scholar 

  • Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia (Berl.)10, 316–323 (1967)

    Google Scholar 

  • Evetts, K. D., Iversen, L. L.: Effects of protriptyline on the depletion of catecholamines induced by 6-hydroxydopamine in the brain of the rat. J. Pharm. Pharmacol.22, 540–543 (1970)

    Google Scholar 

  • Fibiger, H. C., Greewaal, D. S.: Neurochemical evidence for denervation supersensitivity: The effect of unilateral substantia nigra lesions on apomorphine-induced increases in neostriatal acetylcholine levels. Life Sci. 57–63 (1974)

  • Fibiger, H. C., Lonsbury, B., Cooper, H. P.: Early behavioral effects of intraventricular administration of 6-hydroxydopamine in rat. Nature New Biol236, 209–211 (1972)

    Google Scholar 

  • File, S. E., Pope, J. H.: The action of chlorpromazine on exploration in pairs of rats. Psychopharmacologia (Berl.)37, 249–254 (1974)

    Google Scholar 

  • Finch, L.: The cardiovascular effects of intraventricular clonidine and BAY 1470 in conscious hypertensive rats. Brit. J. Pharmacol.52, 333–338 (1974)

    Google Scholar 

  • Haeusler, G.: Clonidine induced inhibition of sympathetic nerve activity: no indication for a central presynaptic or an indirect sympathominetic mode of action. Arch. Pharmacol.286, 97–111 (1974)

    Google Scholar 

  • Hebb, C. O., Krnjevič, K., Silver, A.: Acetylcholine and choline acetyltransferase in the diaphragm of the rat. J. Physiol. (Lond.)171, 504–513 (1964)

    Google Scholar 

  • Herman, Z. S.: The effects of noradrenaline on rat's behaviour. Psychopharmacologia (Berl.)16, 369–374 (1970)

    Google Scholar 

  • Herman, Z. S., Kmieciak-Kolada, K., Brus, R.: Behavior of rats and biogenic amine level in brain after 6-hydroxydopamine. Psychopharmacologia (Berl.)24, 407–416 (1972)

    Google Scholar 

  • Iversen, S. D., Creese, I.: Behavioural correlates of dopaminergic supersensitivity. In: Advances in Neurology, vol. 9. Dopaminergic mechanisms, (D. Calne, T. N. Chase, and A. Barbeau, eds.), pp. 81–92, New York: Raven Press 1975

    Google Scholar 

  • Jackson, D. M.: The involvement of noradrenergic systems in the locomotor activity stimulation in mice produced by β-phenethylamine. J. Pharm. Pharmacol.26, 651–654 (1974)

    Google Scholar 

  • Jalfre, M., Haefely, W.: Effects of some centrally acting agents in rats after intraventricular injections of 6-hydroxydopamine. In: 6-Hydroxydopamine and catecholamine neurons (T. Malmfors and H. Thoenen, eds.), pp. 333–346. Amsterdam: North Holland 1971

    Google Scholar 

  • Janssen, P. A. J., Jageneau, A. H. M., Schellekens, K. H. L.: Chemistry and pharmacology of compounds related to 4-/4-hydroxy-4-phenyl-piperidino-butyrophenone. Part IV. Influence of haloperidol (R 1625) and chlorpromazine on the behaviour of rats in unfamiliar “open field” situation. Psychopharmacologia (Berl.)1, 389–392 (1960)

    Google Scholar 

  • Kim, J. S.: Effects of 6-hydroxydopamine on acetylcholine and GABA metabolism in rat striatum. Brain Res.55, 472–475 (1973)

    Google Scholar 

  • Kobinger, W., Pichler, L.: The central modulatory effect of clonidine on the cardiodepressor reflex after suppression of synthesis and storage of noradrenaline. Europ. J. Pharmacol.30, 56–62 (1975)

    Google Scholar 

  • Kostrzewa, R. M., Jacobowitz, D. M.: Pharmacological actions of 6-hydroxydopamine. Pharmacol. Rev.26, 200–288 (1974)

    Google Scholar 

  • Lal, S., Sourkes, T. L., Missala, K., Belendiuk, G.: Effects of apomorphine and emetine alkaloids on central dopaminergic mechanisms in rats. Europ. J. Pharmacol.20, 71–79 (1972)

    Google Scholar 

  • Liew, M.-Ch., Laverty, R.: Changes in responses to centrally acting drugs in rats treated neonatally with 6-hydroxydopamine. Abstracts of sixth Int. Congress of Pharmacology. Abstract number 1008. 429. Helsinki: University of Helsinki 1975

    Google Scholar 

  • Maj, J., Baran, L., Grabowska, M., Sowińska, H.: Effect of clonidine on the 5-hydroxytryptamine and 5-hydroxyindoleacetic acid brain levels. Biochem. Pharmacol.22, 2679–2683 (1973)

    Google Scholar 

  • Maj, J., Baran, L., Sowińska, H., Zieliński, M.: The influence of cholinolytics on clonidine action. Pol. J. Pharmacol. Pharm.27, 17–26 (1975)

    Google Scholar 

  • Maj, J., Grabowska, M., Gajda, L.: Effect of apomorphine on motility in rats. Europ. J. Pharmacol.17, 208–214 (1972)

    Google Scholar 

  • McKenzie, G. M.: Role of the tuberculum olfactorium in stereotyped behaviour induced by apomorphine in the rat. Psychopharmacologia (Berl.)23, 212–219 (1971)

    Google Scholar 

  • Miller, F. P., Cox, R. H., Jr., Snodgrass, W. R., Maickel, R. P.: Comparative effects ofp-chlorophenylalanine,p-chloroamphetamine andp-chloro-N-methylamphetamine on rat brain norepinephrine, serotonin and 5-hydroxyindole-3-acetic acid. Biochem. Pharmacol.19, 435–442 (1970)

    Google Scholar 

  • Modigh, K.: Electroconvulsive shock and postsynaptic catecholamine effects: Increased psychomotor stimulant action of apomorphine and clonidine in reserpine pretreated mice by repeated ECS. J. neural Transm.36, 19–32 (1975)

    Google Scholar 

  • Moore, K. E., Thornburg, J. E.: Drug induced dopaminergic supersensitivity. In: Advances in neurology, vol. 9. Dopaminergic mechanisms (D. Calne, T. N. Chase, and A. Barbeau, eds.), pp. 93–104. New York: Raven Press 1975

    Google Scholar 

  • Nakamura, K., Thoenen, H.: Increased irritability: A permanent behavior change induced in the rat by intraventricular administration of 6-hydroxydopamine. Psychopharmacologia (Berl.)24, 359–372 (1972)

    Google Scholar 

  • Price, T. C., Fibiger, H.: Apomorphine and amphetamine stereotypy after 6-hydroxydopamine lesions of the substantia nigra. Europ. J. Pharmacol.29, 249–252 (1974)

    Google Scholar 

  • Sachs, Ch., Jonsson, G.: Commentary: Mechanisms of action of 6-hydroxydopamine. Biochem. Pharmacol.24, 1–8 (1975)

    Google Scholar 

  • Scheel-Krüger, J., Hasselager, E.: Studies of various amphetamines, apomorphine and clonidine on body temperature and brain 5-hydroxytryptamine metabolism in rats. Psychopharmacologia (Berl.)36, 189–202 (1974)

    Google Scholar 

  • Ungerstedt, U., Ljungberg, T., Hoffer, B., Siggins, G.: Dopaminergic supersensitivity in the striatum. In: Advances in neurology, vol. 9. Dopaminergic mechanisms (D. Calne, T. N. Chase, and A. Barbeau, eds.), pp. 57–65. New York: Raven Press 1975

    Google Scholar 

  • Yeh, B. H., McNey, T. L., Goldberg, L. I.: Attenuation of dopamine renal and mesenteric vasodilatation by haloperidol: evidence for a specific dopamine receptor. J. Pharmacol. exp. Ther.168, 303–309 (1969)

    Google Scholar 

Download references

Author information

Author notes

  1. Z. S. Herman

    Present address: Department of Pharmacology, Biological-Physiological Institute of Silesian School of Medicine in Katowice, Katowice, Poland

Authors and Affiliations

  1. Department of Pharmacology, Biological-Physiological Institute of Silesian School of Medicine in Katowice, Katowice, Poland

    R. Brus, A. Drybański, R. Szkilnik & J. Słomińska-Żurek

Authors
  1. Z. S. Herman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Brus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Drybański
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Szkilnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Słomińska-Żurek
    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

Herman, Z.S., Brus, R., Drybański, A. et al. Influence of 6-hydroxydopamine on the behavioral effects induced by apomorphine or clonidine in rats. Psychopharmacology 50, 73–80 (1976). https://doi.org/10.1007/BF00634158

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00634158

Key words

Search

Navigation