Abstract
In the present experiments the influence of small acute doses of morphine on rat behaviour was investigated. Small doses of morphine produced stimulation of locomotion, rearing, grooming, eating and drinking. Inhibition of catecholamine biosynthesis by α-methyl tyrosine and FLA-63 or blockade of the catecholamine receptors in the brain could inhibit the behavioral stimulant effects of morphine. Comparison between the morphine-induced hyperactivity and the stimulation of behaviour by amphetamine showed that the behavioural profiles of the excitation produced by these drugs differ significantly from each other, and it was concluded that morphine stimulates the behaviour of rats probably by a different mechanism from that of amphetamine.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
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, 303–314 (1970).
Andén, N.-E., Corrodi, H., Fuxe, K.: Effect of neuroleptic drugs on central catecholamine turnover assessed using tyrosine- and dopamine-Β-hydroxylase inhibitors. J. Pharm. Pharmacol. 24, 177–182 (1972).
Ayhan, I. H.: Effect of 6-hydroxydopamine on morphine analgesia. Psychopharmacologia (Berl.) 25, 183–188 (1972).
Ayhan, I. H., Randrup, A.: Role of brain noradrenaline in morphine-induced stereotyped behaviour. Psychopharmacologia (Berl.) 27, 203–212 (1972).
Carlsson, A.: Amphetamine and brain catecholamines. In: Amphetamine and related compounds. E. Costa and S. Garattini, eds., pp. 289–300. New York: Raven Press 1970.
Carlsson, A., Lindqvist, M., Magnusson, T.: 3,4-Dihydroxyphenylalanine and 5-hydroxytryptamine as reserpine antagonists. Nature (Lond.) 180, 1200 (1957).
Carlsson, A., Lindqvist, M., Dahlström, A., Fuxe, K., Masuoka, D.: Effects of amphetamine group on intraneuronal brain amines in vivo and in vitro. J. Pharm. Pharmacol. 17, 521–524 (1965).
Carr, L. A., Moore, K. E.: Norepinephrine: Release from brain by d-amphetamine in vivo. Science 164, 322–323 (1969).
Corrodi, H., Hanson, L. C. F.: Central effects of an inhibitor of tyrosine hydroxylation. Psychopharmacologia (Berl.) 10, 116–125 (1966).
Costall, B., Naylor, R. J., Wright, T.: The use of amphetamine induced stereotyped behaviour as a model for the experimental evaluation of antiparkinson agents. Arzneimittel-Forsch. (Drug Res.) 22, 1178–1183 (1972).
Fog, R.: Behavioural effects in rats of morphine and amphetamine and of a combination of the two drugs. Psychopharmacologia (Berl.) 16, 305–312 (1970).
Fukui, K., Takagi, H.: Effect of morphine on the cerebral contents of metabolites of dopamine in normal and tolerant mice: its possible relation to analgesic action. Brit. J. Pharmacol. 44, 45–51 (1972).
Fukui, K., Shiomi, H., Takagi, H.: Effects of morphine on tyrosine hydroxylase activity in mouse brain. Europ. J. Pharmacol. 19, 123–125 (1972).
Fuxe, K., Ungerstedt, U.: Histochemical, biochemical and functional studies on central monoamine neurons after acute and chronic amphetamine administration. In: Amphetamine and related compounds, E. Costa and S. Garattini, eds., pp. 257–288. New York: Raven Press 1970.
Gunne, L.-M.: Catecholamines and 5-hydroxytryptamine in morphine tolerance and withdrawal. Acta physiol. scand. Suppl. 204, 1–91 (1963).
Gunne, L.-M., Jönsson, J., Fuxe, K.: Effects of morphine intoxication on brain catecholamine neurons. Europ. J. Pharmacol. 5, 338–342 (1969).
Hanson, L. C. F.: Evidence that the central action of (+)-amphetamine is mediated via catecholamines. Psychopharmacologia (Berl.) 10, 289–297 (1967).
Hollinger, M.: Effect of reserpine, α-methyl-p-tyrosine, p-chlorophenylalanine and pargyline on levorphanol-induced running activity in mice. Arch. int. Pharmacodyn. 179, 419–424 (1969).
Janssen, P. A., Niemegeers, C. J., Sohellekens, K. H. L.: Is it possible to predict the clinical effects of neuroleptic drugs (major tranquilizers) from animals data (part I). Arzneimittel-Forsch. (Drug Res.) 15, 104–117 (1965).
Janssen, P. A., Niemegeers, C. J., Schellekens, K. H. L.: Is it possible to predict the clinical effects of neuroleptic drugs (major tranquilizers) from animal data (part IV). Arzneimittel-Forsch. (Drug Res.) 17, 841–854 (1967).
Katz, D. M., Steinberg, H.: Long-term isolation in rats reduces morphine response. Nature (Lond.) 228, 469–471 (1970).
Kumar, R., Mitchell, E., Stolerman, I. P.: Disturbed patterns of behaviour in morphine tolerant and abstinent rats. Brit. J. Pharmacol. 42, 473–484 (1971).
Kuschinsky, K., Hornykiewicz, O.: Morphine catalepsy in the rat: relation to striatal dopamine metabolism. Europ. J. Pharmacol. 19, 119–122 (1972).
Laverty, R., Sharman, D. F.: Modification by drugs on the metabolism of 3,4-dihydroxyphenylethylamine, noradrenaline and 5-hydroxytryptamine in the brain. Brit. J. Pharmacol. 24, 759–772 (1965).
McKenzie, G. M., Szerb, J. C.: The effect of dihydroxyphenylalanine, pheniprazine and dextroamphetamine on the in vivo release of dopamine from the caudate nucleus. J. Pharmacol. exp. Ther. 162, 302–308 (1968).
Papeschi, R., Randrup, A.: Catalepsy, sedation and hypothermia induced by alpha-methyl-p-tyrosine in the rat. An ideal tool for screening of drugs active on central catecholaminergic receptors. (Submitted for publication.) (1973).
Quinton, R. M., Halliwell, G.: Effects of α-methyl DOPA and DOPA on the amphetamine excitatory response in reserpinized rats. Nature (Lond.) 200, 178–179 (1963).
Randrup, A., Munkvad, I.: Role of catecholamines in the amphetamine excitatory response. Nature (Lond.) 211, 540 (1966).
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.
Randrup, A., Mundvad, I.: Correlation between specific effects of amphetamines on the brain and on behaviour. Symposium on current concepts on amphetamine abuse. Duke University 1970. E. H. Ellinwood, Jr., ed. (in press).
Reis, D. J., Rifkin, M., Corvelli, A., Effects of morphine on cat brain norepinephrine in regions with daily monoamine rhythms. Europ. J. Pharmacol. 8, 149–152 (1969).
Rethy, C. R., Smith, C. B., Villarreal, J. E.: Effects of narcotic analgesics upon the locomotor activity and brain catecholamine content of the mouse. J. Pharmacol. exp. Ther. 176, 472–479 (1971).
Roffler-Tarlov, S., Sharman, D. F., Tegerdine, P.: Dihydroxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetic acid in the mouse striatum: A reflection of intra- and extra-neuronal metabolism of dopamine? Brit. J. Pharmacol. 42, 343–351 (1971).
Ross, S. B., Renyi, A. L.: Inhibition of the uptake of tritiated catecholamines by antidepressant and related agents. Europ. J. Pharmacol. 2, 181–186 (1967).
SchiØrring, E.: Amphetamine induced selective stimulation of certain behaviour items with concurrent inhibition of others in an open-field test with rats. Behaviour 39, 1–17 (1971).
SchiØrring, E., Hecht, A.: Behavioural responses of non-tolerant rat groups to the administration of 2 mg/kg morphine in an open-field test. (In preparation.)
SchiØrring, E., Randrup, A.: Social isolation and changes in the formation of groups induced by amphetamine in an open-field test with rats. Pharmakopsychiatrie. Neuro-Psychopharmakol. 4, 2–11 (1971).
Sloan, J. W., Brooks, J. W., Eisenman, A. J., Martin, E. R.: The effect of addiction to and abstinence from morphine on rat tissue catecholamine and serotonin levels. Psychopharmacologia (Berl.) 4, 261–270 (1963).
Smith, C. B., Sheldon, M. I., Bednarczyk, J. H., Villarreal, J. E.: Morphine-induced increases in the incorporation of 14C-tyrosine into 14C-dopamine and 14C-norepinephrine in the mouse brain: Antagonism by naloxone and tolerance. J. Pharmacol. exp. Ther. 180, 547–557 (1972).
Snedecor, G. W.: Statistical methods, 5th ed., pp. 97. Ames Iowa: The Iowa State Univ. Press 1956.
Strömberg, U., Svensson, T. H.: l-DOPA induced effects on motor activity in mice after inhibition of dopamine-Β-hydroxylase. Psychopharmacologia (Berl.) 19, 53–60 (1971).
Svensson, T. H.: The effect of inhibition of catecholamine synthesis on dexamphetamine induced central stimulation. Europ. J. Pharmacol. 12, 161–166 (1970).
Takagi, H., Kuriki, H.: Suppressive effect of tetrabenazine on the development of tolerance to morphine and its reversal by DOPA. Int. J. Neuropharm. 8, 195–196 (1969).
Takagi, H., Nakama, M.: Effect of morphine and nalorphine on the content of dopamine in mouse brain. Jap. J. Pharmacol. 16, 483–484 (1966).
Taylor, K. M., Snyder, S. H.: Differential effects of d- and l-amphetamine on behaviour and on catecholamine disposition in dopamine and norepinephrine containing neurons of rat brain. Brain Res. 28, 295–309 (1971).
Van Nueten, J. M.: Etude des effects de dérives phénothiaziniques et butyrophénoniques sur l'action amphetamine chez le rat. Thesis, Paris 1962.
Vogt, M.: Concentration of sympathin in different parts of the central nervous system under normal conditions and after administration of drugs. J. Physiol. (Lond.) 123, 451–481 (1954).
Ziegler, H., Del Basso, P., Longo, V. G.: Influence of 6-hydroxydopamine and α-methyl-p-tyrosine on the effects of some centrally acting agents. Physiol. Behav. 8, 391–396 (1972).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ayhan, I.H., Randrup, A. Behavioural and pharmacological studies on morphine-induced excitation of rats. Possible relation to brain catecholamines. Psychopharmacologia 29, 317–328 (1973). https://doi.org/10.1007/BF00429279
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00429279