Skip to main content
Log in

Drug-induced rotation in rats without lesions: Behavioral and neurochemical indices of a normal asymmetry in nigro-striatal function

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

Abstract

Normal unoperated rats were tested for rotation (i.e., circling behavior) in a spherical “rotometer” and dose-response relationships were generated using d-amphetamine, apomorphine, L-Dopa, haloperidol, and scopolamine. The rotation induced by amphetamine was significantly antagonized by alphamethyl-p-tyrosine and haloperidol, but not by diethyl-dithiocarbamate. The rotation elicited by apomorphine was unaffected by alpha-methyl-p-tyrosine. Rotation was not necessarily in the same direction with high and low doses of amphetamine, or amphetamine and apomorphine administered a week apart from each other. Dopaminergic-cholinergic interactions were evident, since pilocarpine antagonized amphetamine-induced rotation whereas scopolamine did not; scopolamine elicited rotation in the same direction as that induced by amphetamine. Left and right striatal dopamine and tel-diencephalic norepinephrine levels were determined in rats injected with various doses of amphetamine and tested for rotation. There were significant bilateral differences in striatal dopamine which were related to the direction of rotation. Since amphetamine was found to be equally distributed to the two sides of the brain, the difference in striatal dopamine appeared to be the neurochemical substrate for rotation in normal rats. These results suggest that normal rats have asymmetrical levels of striatal dopamine as well as an asymmetrical complement of striatal dopamine receptors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Andén, N. E.: Effects of amphetamine and some other drugs in central catecholamine mechanisms. In: Amphetamines and related compounds, E. Costa and S. Garattini, eds., pp. 447–462. New York: Raven Press 1970

    Google Scholar 

  • Andén, N. E., Bedard, P.: Influences of cholinergic mechanisms on the function and turnover of brain dopamine. J. Pharm. Pharmacol. 23, 460–462 (1971)

    Google Scholar 

  • Andén, N. E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and norepinephrine after neuroleptics. Europ. J. Pharmacol. 11, 303–314 (1970)

    Google Scholar 

  • Andén, N. E., Dahlstrom, A., Fuxe, K., Larsson, K.: Functional role of the nigro-neostriatal dopamine neurons. Acta pharmacol. et Toxicol 24, 263–274 (1966)

    Google Scholar 

  • Anggard, E., Gunne, L. M., Niklasson, F.: Gas chromatographic determination of amphetamine in blood, tissue, and urine. J. Scand. Clin. Lab. Invest. 26, 137–143 (1970)

    Google Scholar 

  • Arbuthnott, G. W., Crow, T. J.: Relation of contraversive turning to unilateral release of dopamine from the nigro-striatal pathway in rats. Exp. Neurol. 30, 484–491 (1971)

    Google Scholar 

  • Axelrod, J.: Amphetamine: metabolism, physiological disposition and its effects on catecholamine storage. In: Amphetamines and related compounds, E. Costa and S. Garattini, eds., pp. 207–215. New York: Raven Press 1970

    Google Scholar 

  • Bak, I. J., Hassler, R., Kim, J. S., Kataoka, K.: Amantadine actions on acetylcholine and GABA in striatum and substantia nigra of rat in relation to behavioral changes. J. neural Trans. 33, 45–61 (1972)

    Google Scholar 

  • Bartholini, G., Pletscher, A.: Drugs affecting monoamines in the basal ganglia. Advanc. Biochem. Psychopharmacol. 6, 135–148 (1972)

    Google Scholar 

  • Brodie, B. B., Cho, A. K., Gessa, G. L.: Possible role of p-hydroxynorephedrine in the depletion of norepinephrine, induced by d-amphetamine and in tolerance to this drug. In: Amphetamine and related compounds, E. Costa and S. Garattini, eds., pp. 217–229. New York: Raven Press 1970

    Google Scholar 

  • Buchwald, N. A., Wyers, E. J., Lauprecht, C. W., Heuser, G.: The “caudate-spindle”. IV. A behavioral index of caudate-induced inhibition. Electroenceph. clin. Neurophysiol. 13, 531–537 (1961)

    Google Scholar 

  • Bunney, B. S., Aghajanian, G. K., Roth, R. H.: Comparison of the effects of L-Dopa, amphetamine and apomorphine on the firing rate of rat dopaminergic neurons. Nature New Biol. 245, 123–125 (1973)

    Google Scholar 

  • Carlsson, A., Lindqvist, M., Fuxe, K., Hokfelt, T.: Histochemical and biochemical effects of diethyldithiocarbamate on tissue catecholamines. J. Pharm. Pharmacol. 18, 60–62 (1966)

    Google Scholar 

  • Christie, J. E., Crow, T. J.: Turning behavior as an index of the action of amphetamine and ephedrines on central dopamine-containing neurons. Brit. J. Pharmacol. 43, 658–667 (1971)

    Google Scholar 

  • Collins, G. G. S.: Inhibition of dopamine-beta-hydroxylase by diethyldithiocarbamate. J. Pharm. Pharmacol. 17, 526–527 (1965)

    Google Scholar 

  • Corrodi, H., Fuxe, K., Hamberger, B., Ljungdahl, A.: Studies on central and peripheral noradrenaline neurons using a new dopamine-beta-hydroxylase inhibitor. Europ. J. Pharmacol. 12, 145–155 (1970)

    Google Scholar 

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

    Google Scholar 

  • Costall, B., Naylor, R. J., Olley, J. E.: Catalepsy and circling behavior after intracerebral injections of neuroleptic, cholinergic and anticholinergic agents into the caudate-putamen, globus pallidus and substantia nigra of rat brain. Neuropharmacology 11, 645–663 (1972)

    Google Scholar 

  • Costall, B., Olley, J. E.: Cholinergic and neuroleptic induced catalepsy: modification by lesions in the globus pallidus and substantia nigra. Neuropharmacology 10, 581–591 (1971)

    Google Scholar 

  • Crow, T. J.: The relationship between lesion site dopamine neurons, and turning behavior in the rat. Exp. Neurol 32, 247–255 (1971)

    Google Scholar 

  • Dominic, J. A., Moore, K. E.: Supersensitivity to the central stimulant actions of adrenergic drugs following discontinuation of a chronic diet of a-methyl-tyrosine. Psychopharmacologia (Berl.) 15, 96–101 (1969)

    Google Scholar 

  • Ernst, A. M.: Relation between the action of dopamine and apomorphine and their O-methylated derivates upon the CNS. Psychopharmacologia (Berl.) 7, 391–399 (1965)

    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 

  • Gianutsos, G., Drawbaugh, R. B., Hynes, M. D., Lal, H.: Behavioral evidence for dopaminergic supersensitivity after chronic haloperidol. Life Sci. 14, 887–889 (1974)

    Google Scholar 

  • Glick, S. D., Greenstein, S.: Possible modulating influence of frontal cortex on nigro-striatal function. Brit. J. Pharmacol. 49, 316–321 (1973)

    Google Scholar 

  • Glick, S. D., Jerussi, T. P., Waters, D. H., Green, J. P.: Amphet-amine-induced changes in striatal dopamine and acetylcholine levels in relationship to rotation (circling behavior) in rats. Biochem. Pharmacol. 23, 3223–3225 (1974)

    Google Scholar 

  • Goldstein, M.: Inhibition of norepinephrine at the dopamine-beta-hydroxylation stage. Pharmacol. Rev. 18, 77–82 (1966)

    Google Scholar 

  • Goldstein, M., Freeman, L. S., Backstrom, T.: The inhibition of catecholamine biosynthesis by apomorphine. J. Pharm. Pharmacol. 22, 715–717 (1970)

    Google Scholar 

  • Greenstein, S., Glick, S. D.: Improved automated apparatus for recording rotation (circling behavior) in rats or mice. Pharmacol. Biochem. Behav. 3, 507–510 (1975)

    Google Scholar 

  • Harris, J. E., Baldessarini, R. J., Roth, R. H.: Amphetamine-induced inhibition of tyrosine hydroxylation in homogenates of rat corpus striatum. Neuropharmacology 14, 457–471 (1975)

    Google Scholar 

  • Jerussi, T. P., Glick, S. D.: Amphetamine-induced rotation in rats without lesions. Neuropharmacology 13, 283–286 (1974)

    Google Scholar 

  • Jerussi, T. P., Glick, S. D.: Apomorphine-induced rotation in normal rats and interaction with unilateral caudate lesions. Psychopharmacologia (Berl.) 40, 329–334 (1975)

    Google Scholar 

  • Keller, H. H., Bartholini, G., Pletscher, A.: Drug-induced changes of striatal cholinergic and dopaminergic functions in rats with spreading depression. J. Pharm. Pharmacol. 25, 433–436 (1973)

    Google Scholar 

  • Kirby, R. J.: Caudate nucleus and arousal in the rat. J. comp. physiol. Psychol. 85, 82–96 (1973)

    Google Scholar 

  • Kuczenski, R.: Effects of catecholamine releasing agents on synaptosomal dopamine biosynthesis: multiple pools of dopamine or multiple forms of tyrosine hydroxylase. Neuropharmacology 14, 1–10 (1975)

    Google Scholar 

  • Laverty, R., Taylor, K. M.: The fluorometric assay of catecholamines and related compounds. Analyt. Biochem. 22, 269–279 (1968)

    Google Scholar 

  • Leonard, B. E., Shallice, S. A.: Some neurochemical effects of amphetamine, methylamphetamine and p-bromomethylamphetamine in the rat. Brit. J. Pharmacol. 41, 198–212 (1971)

    Google Scholar 

  • Lippman, W., Lloyd, K.: Dopamine-beta-hydroxylase inhibition by dimethyldithiocarbamate and related compounds. Biochem. Pharmacol. 18, 2507–2516 (1969)

    Google Scholar 

  • Marsden, C. A., Guldberg, H. C.: The role of monoamines in rotation induced or potentiated by amphetamine after nigral, raphe and mesencephalic reticular lesions in the rat brain. Neuropharmacology 12, 195–224 (1973)

    Google Scholar 

  • McKenzie, G. M., Gordon, R. J., Vilk, K.: Some biochemical and behavioral correlates of a possible animal model of human hyperkinetic syndromes. Brain Res 47, 439–456 (1972)

    Google Scholar 

  • Mennear, J. H.: Interactions between central cholinergic agents and amphetamine in mice. Psychopharmacologia (Berl.) 7, 107–114 (1965)

    Google Scholar 

  • Muller, P., Seeman, P.: Neuroleptics: A relation between cataleptic and anti-turning actions, and role of the cholinergic system. J. Pharm. Pharmacol. 26, 981–984 (1974)

    Google Scholar 

  • Naylor, R. J., Olley, J. E.: Modification of the behavioral changes by amphetamine in the rat by lesions of the caudate nucleus, the caudate-putamen and globus pallidus. Neuropharmacology 11, 91–99 (1972)

    Google Scholar 

  • Noonan, J. S., Murdick, P. W., Ray, R. S.: A method for detecting amphetamine using gas chromatography of a halogenated derivative. J. Pharmacol. exp. Ther. 168, 205–209 (1968)

    Google Scholar 

  • Overstreet, D. H., Vasquez, B. J., Russell, R. W.: Reduced behavioural effects of intrahippocampally administered carbachol in rats with low cholinesterase activity. Neuropharmacology 13, 911–917 (1974)

    Google Scholar 

  • Potegal, M.: Role of the caudate nucleus in spatial orientation of rats. J. comp. physiol. Psychol. 69, 756–764 (1969)

    Google Scholar 

  • Sethy, V. H., Van Woert, M. H.: Modification of striatal acetylcholine concentration by dopamine receptor agonists and antagonists. Res. Comm. chem. Path. Pharmacol. 8, 13–28 (1974)

    Google Scholar 

  • Smith, C. B.: Effects of d-amphetamine upon brain amine content and locomotor activity of mice. J. Pharmacol. exp. Ther. 147, 96–102 (1965)

    Google Scholar 

  • Snyder, S. H., Taylor, K. M.: Assay of biogenic amines and their deaminating enzymes in animal tissue. In: Research methods in neurochemistry, N. Marks and R. Rodnight, eds., pp. 287–315. New York: Plenum Press 1972

    Google Scholar 

  • Spector, S., Sjoerdsma, A., Udenfriend, S.: Blockade of endogenous norepinephrine synthesis by alpha-methyl-tyrosine an inhibitor of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 147, 86–95 (1965)

    Google Scholar 

  • Tarsy, D., Baldessarini, R. J.: Behavioral supersensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic functions of catecholamines. Neuropharmacology 13, 927–940 (1974)

    Google Scholar 

  • Ungerstedt, U.: Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behavior. Acta physiol. scand., Suppl. 367, 49–68 (1971a)

    Google Scholar 

  • Ungerstedt, U.: Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta physiol. scand., Suppl. 367, 69–93 (1971b)

    Google Scholar 

  • Ungerstedt, U., Arbuthnott, G. W.: Quantitative recording of rotational behavior in rats after 6-hydroxydopamine lesions of the nigro-striatal dopamine system. Brain Res. 24, 485–493 (1970)

    Google Scholar 

  • Ungerstedt, U., Butcher, L. L., Butcher, S. G., Andén, N. E., Fuxe, K.: Direct chemical stimulation of dopaminergic mechanisms in the neostriatum of the rat. Brain Res. 14, 461–471 (1969)

    Google Scholar 

  • Volle, R. L., Koelle, G. B.: Ganglionic stimulating and blocking agents. In: The pharmacological basis of therapeutics, L. S. Goodman and A. Gilman, eds., pp. 585–600. New York: McMillan 1970

    Google Scholar 

  • Walters, J. R., Roth, R. H.: Dopaminergic neurons: drug-induced antagonism of the increase in tyrosine hydroxylase activity produced by cessation of impulse flow. J. Pharm. Pharmacol. 191, 82–91 (1974)

    Google Scholar 

  • Weil-Malberbe, H.: The chemical estimation of catecholamines and their metabolites in body fluids and tissue extracts. In: Analysis of biogenic amines and their related enzymes, D. G. Glick, ed., pp. 119–152. New York: Interscience Publishers 1971

    Google Scholar 

  • Weissman, A., Koe, B. K., Tenen, S. S.: Anti-amphetamine effects following inhibition of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 151, 339–352 (1966)

    Google Scholar 

  • Zimmerberg, B., Glick, S. D., Jerussi, T. P.: Neurochemical correlate of a spatial preference in rats. Science 185, 623–625 (1974)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jerussi, T.P., Glick, S.D. Drug-induced rotation in rats without lesions: Behavioral and neurochemical indices of a normal asymmetry in nigro-striatal function. Psychopharmacology 47, 249–260 (1976). https://doi.org/10.1007/BF00427609

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00427609

Key words

Navigation