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A functional effect of dopamine in the nucleus accumbens and in some other dopamine-rich parts of the rat brain

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Abstract

Dopamine (5 to 50 Μg) applied bilaterally to the nucleus accumbens of reserpine-nialamide pretreated rats produced a marked dose-dependent rise in coordinated locomotor activity, devoid of stereotypies such as gnawing, rearing and licking seen after dopamine application (50 Μg) to the neostriatum. The locomotor activity was completely blocked by pimozide, but not by phenoxybenzamine. The effects of apomorphine or d-noradrenaline were similar to those of dopamine. In contrast, l-noradrenaline produced a “convulsive” syndrome devoid of coordinated locomotor activity, and this convulsive syndrome could be completely blocked by phenoxybenzamine but not by pimozide. Release of endogenous dopamine by d- or l-amphetamine (10 and 50 Μg) in the nucleus accumbens produced a rise in coordinated activity, the d-isomer was about 4 times as potent as the l-isomer, and the effect of the d-isomer was blocked completely by α-methyltyrosine. Bilateral application of trifluoperazine (2.5 Μg) to the nucleus accumbens completely blocked the effect of systemically administered d-amphetamine (1.5 and 3.0 mg/kg), but similar application to the area of the central nucleus of the amygdala or the neostriatum was much less effective. Partial protection of the endogenous dopamine stores against the depleting action of reserpine by local application of metatyramine to the nucleus accumbens resulted in a higher level of basal activity than in control animals. Application of dopamine or noradrenaline to the area of the central nucleus of the amygdala or to the olfactory tubercles did not lead to any consistent changes in locomotor activity.

The nucleus accumbens and olfactory tubercles contained most of the dopamine in the limbic forebrain, with noradrenaline more evenly distributed.

These data suggest that the nucleus accumbens plays an important role in the locomotor activity in rats.

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References

  • Andén, N.-E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol. 11, 303–312 (1970a)

    Google Scholar 

  • Andén, N.-E., Butcher, S. G., Fuxe, K.: Protection of the neostriatal dopamine stores against reserpine by local treatment with metatyramine. Acta pharmacol. (Kbh.) 28, 39–48 (1970b)

    Google Scholar 

  • Andén, N.-E., Fuxe, K., Hamberger, B., Hökfelt, T.: A quantitative study of the nigro-neostriatal dopamine neuron system. Acta physiol. scand. 67, 306–312 (1966a)

    Google Scholar 

  • Andén, N.-E., Jukes, M. G. M., Lundberg, A.: The effect of DOPA on the spinal cord. 2. A pharmacological analysis. Acta physiol. scand. 67, 387–397 (1966b)

    Google Scholar 

  • Atack, C. V.: The determination of dopamine by a modification of the dihydroxyindole fluorimetric assay. Brit. J. Pharmacol. 48, 699–714 (1973)

    Google Scholar 

  • Atack, C. V., Magnusson, T.: Individual elution of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from a single, strong cation exchange column, by means of mineral acid-organic acid solvent mixtures. J. Pharm. Pharmacol. 22, 625–627 (1970)

    Google Scholar 

  • Benkert, O.: Measurement of hyperactivity in rats in a doseresponse curve after intrahypothalamic norepinephrine injection. Life Sci. 8, 943–948 (1969)

    Google Scholar 

  • Benkert, O., Köhler, B.: Intrahypothalamic dopamine and norepinephrine injections in relation to motor hyperactivity in rats. Psychopharmacologia (Berl.) 24, 318–325 (1972)

    Google Scholar 

  • De Maio, D.: Clozapine, a novel major tranquilliser. Arzneimittel-Forsch. 22, 919–923 (1972)

    Google Scholar 

  • Fog, R., Randrup, A., Pakkenberg, H.: Lesions in the corpus striatum and cortex of rat brains and the effect on pharmacologically induced stereotyped, aggressive and cataleptic behaviour. Psychopharmacologia (Berl.) 18, 346–356 (1970)

    Google Scholar 

  • Fuxe, K.: Evidence for the existence of monoamine neurons in the central nervous system. IV. Distribution of monoamine nerve terminals in the central nervous system. Acta physiol. scand. 64, Suppl. 247, 39–85 (1965)

    Google Scholar 

  • Fuxe, K., Ungerstedt, U.: Histochemical, biochemical and functional studies on central monoamine neurons after acute and chronic amphetamine administration. In: Amphetamines and related compounds, E. Costa and S. Garattini, eds., pp. 257–288. New York: Raven Press 1970

    Google Scholar 

  • Gessa, G. L., Krishna, G., Forn, J., Tagliamonte, A., Brodie, B. B.: Behavioural and vegetative effects produced by dibutyryl cyclic AMP injected into different areas of the brain. In: Role of cyclic AMP in cell function, P. Greengard and E. Costa, eds., pp. 371–381. Advances in biochemical psychopharmacology, Vol. 3. New York: Raven Press 1970

    Google Scholar 

  • HÄggendal, J.: An improved method for fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissues. Acta physiol. scand. 59, 242–254 (1963)

    Google Scholar 

  • Hanson, L. C. F.: Evidence that the central action of amphetamine is mediated via catecholamines. Psychopharmacologia (Berl.) 9, 78–80 (1966)

    Google Scholar 

  • Hanson, L. C. F.: Evidence that the central action of (+)-amphetamine is mediated via catecholamines. Psychopharmacologia (Berl.) 10, 289–297 (1967)

    Google Scholar 

  • Herman, Z. S.: Behavioural effects of dibutyryl cyclic 3′,5′-AMP, noradrenaline and cyclic 3′,5′AMP in rats. Neuropharmacol. 12, 705–709 (1973)

    Google Scholar 

  • Horn, A. S., Cuello, A. C., Miller, R. J.: Dopamine in the mesolimbic system of the rat brain: endogenous levels and the effects of drugs on the uptake mechanism and stimulation by adenylate cyclase activity. J. Neurochem. 22, 265–270 (1974)

    Google Scholar 

  • Jackson, D. M.: The effect of Β-phenylethylamine upon spontaneous motor activity in mice: Demonstration of a dual effect on motor activity, J. Pharm. Pharmacol. 24, 383–389 (1972)

    Google Scholar 

  • Jackson, D. M.: Β-Phenylethylamine and locomotor activity in mice: Interaction with catecholaminergic neurones and receptors. Arzneimittel-Forsch. 25, 622–626 (1975)

    Google Scholar 

  • Jackson, D. M., Temple, D. M.: Β-Phenylethylamine as a cardiotonic constituent of tissue extracts. Comp. gen. Pharmacol. 1, 155–159 (1970)

    Google Scholar 

  • Janssen, P. A. J., Niemegeers, C. J. E., Schellekers, K. H. L., Dresse, A., Lenaerts, F. M., Pinchard, A., Schaper, W. K. A., van Nueton, J. M., Verbruggen, F. J.: Pimozide, a chemically novel, highly potent and orally long-acting neuroleptic drug. Arzneimittel-Forsch. 18, 261–287 (1968)

    Google Scholar 

  • Jonsson, J., Grobecker, H., Holtz, P.: Effect of Β-phenylethylamine on content and subcellular distribution of norepinephrine in rat heart and brain. Life Sci. 5, 2235–2246 (1966)

    Google Scholar 

  • Kebabian, J. W., Petzold, G. L., Greengard, P.: Dopaminesensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the “dopamine receptor”. Proc. nat. Acad. Sci. (Wash.) 69, 2145–2149 (1972)

    Google Scholar 

  • König, J. F. R., Klippel, R. A.: The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. Baltimore: Williams and Wilkins 1963

    Google Scholar 

  • Lorens, S. A., Sorensen, J. P., Harvey, J. A.: Lesions in the nuclei accumbens septi of the rat: Behavioural and neurochemical effects. J. comp. physiol. Psychol. 73, 284–290 (1970)

    Google Scholar 

  • Malec, D., Kleinrok, Z.: The spontaneous motility of rats after intraventricular injection of dopamine. Neuropharmacol. 11, 331–336 (1972)

    Google Scholar 

  • Nakajima, T., Kakimoto, Y., Sano, I.: Formation of Β-phenylethylamine in mammalian tissue and its effects on motor activity in the mouse. J. Pharmacol. exp. Ther. 143, 319–325 (1964)

    Google Scholar 

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

    Google Scholar 

  • Pijnenburg, A. J. J., van Rossum, J. M.: Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens. J. Pharm. Pharmacol. 25, 1003–1005 (1973)

    Google Scholar 

  • Pijnenburg, A. J. J., Woodruff, G. N., van Rossum, J. M.: Ergometrine induced locomotor activity following intracerebral injection into the nucleus accumbens. Brain Res. 59, 289–302 (1973)

    Google Scholar 

  • Randrup, A., Munkvad, I.: Role of catecholamines in the amphetamine excitatory response. Nature (Lond.) 211, 540 (1966)

    Google Scholar 

  • Randrup, A., Munkvad, I.: Biochemical, anatomical and psychological investigations of stereotyped behaviour induced by amphetamines. In: Amphetamines and related compounds, E. Costa and S. Garattini, eds., pp. 695–713. New York: Raven Press 1970

    Google Scholar 

  • Sabelli, H. C., Mosnaim, A. D.: Phenylethylamine hypothesis of affective behaviour. Amer. J. Psychiat. 131, 695–699 (1974)

    Google Scholar 

  • Scheel-Krüger, J.: Behavioural and biochemical comparison of amphetamine derivatives, cocaine, benztropine and tricyclic antidepressant drugs. Europ. J. Pharmacol. 18, 63–73 (1972)

    Google Scholar 

  • Segal, D. S., Mandell, A. J.: Behavioural activation of rats during intraventricular infusion of norepinephrine. Proc. nat. Acad. Aci. (Wash.) 66, 289–293 (1970)

    Google Scholar 

  • Smith, C. B.: Enhancement by reserpine and α-methyl DOPA of the effects of d-amphetamine upon the locomotor activity of mice. J. Pharmacol. exp. Ther. 142, 343–350 (1963)

    Google Scholar 

  • Stille, G., Hippius, H.: Kritische Stellungnahme zum Begriff der Neuroleptika (anhand von pharmakologischen und klinischen Befunden mit Clozapin). Pharmakopsychiat. Neuropsychopharmak. 4, 182–191 (1971)

    Google Scholar 

  • Stone, E. A., Mendlinger, S.: Effect of intraventricular amines on motor activity in hypothermic rats. Res. Commun. Chem. Path. Pharmacol. 7, 549–556 (1974)

    Google Scholar 

  • Svensson, T. H.: Functional and biochemical effects of d-and l-amphetamine on central catecholamine neurons. Naunyn-Schmiedebergs Arch. Pharmak. 271, 170–180 (1971)

    Google Scholar 

  • Svensson, T. H., Thieme, G.: An investigation of a new instrument to measure motor activity of small animals. Psychopharmacologia (Berl.) 14, 157–163 (1969)

    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 

  • Weissman, A., Koe, B. K.: Behavioural effects of l-α-methyl tyrosine, an inhibitor of tyrosine hydroxylase. Life Sci. 4, 1037–1048 (1965)

    Google Scholar 

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Jackson, D.M., Andén, NE. & Dahlström, A. A functional effect of dopamine in the nucleus accumbens and in some other dopamine-rich parts of the rat brain. Psychopharmacologia 45, 139–149 (1975). https://doi.org/10.1007/BF00429052

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