Effects of 6-Hydroxydopamine and L-Dopa on Amphetamine-Induced Increase in Motor Activity in Rats

Year 1971, Volume: 24 Issue: 6, 1060 - 1073, 31.12.1971

İsmail Ulus

Abstract

In the present study, we tested the interaction of 6-OHDA and/or L-DOPA with d-amphetamine on the motor activity of rats. The motor activity was measured in (Y) maze during the 10 minutes, 45 minutes after the injection of amphetamine intraperitonealy. d-Amphetamine sülphate increased the snontaneous motor activity of rats in a dose dependent manner, Spontaneous motor activity increased from a control response of 4.550.5 to 14.752.6, 42.6F4.2 and 54.155.8 after the injection of 0.5, 1 and 1.5 mg/kg d-amphetamine respectively. Stereotyped behaviours such as Ssnif. fing and licking began with 2.5 mg/kg d-ampheamine Stereotyped behaviours masked locomotor activity so that it decreased after 2.5 mg/kg of d-amphetamine (Fig — 1). The effect of 1 mg/kg of d-ampheamine on the motor activity of rats which recievel L-DOPA (50 mg/kg perday for 7 days) was significantiy lower than control animals, (p < 0.05). 250 ug 6-OHDA, which was injected intracerebroventricularIy three days before the test, caused an increase on the effect of 1mg/kg of d-amphetamine on the motor activity of rats. Spontoneous motor activity increased from 37.5 - 7.5 to 69.7 -9.1 with 1 mg/kg of d-amphetamine. (p<0.01) On the contrary, the increase which was produced by the same dose of amphetamine wasn't different than control animals, after 30 days from 6-OHDA injection. Another group of rats, which was treated with 50 mg/kg i.p L-DOPA for 7 days, given 250 ug of 6-OHDA intracerebroventricularly at the seventh day and tested with 1 mg/kg of d-ampheamine after 3 days 6-OHDA injection. The amphetamine response in these rats wasn't different from control rats. The results has been discussed considering the role of central monoaminergic system on regulation of motor activity and effects of drugs on this system,

Keywords

Motor activity , 6-OHDA , L-DOPA

Amfetamin'in Sıçanda Meydana Getirdiği Motor Aktivite Artışına 6-Hidroksidopamin ve L-Dopa'nın Etkileri

Abstract

Bu çalışmada, sıçanlarda motor aktivite üzerinde, 6-OHDA ve L-DOPA'nın ayrı ayrı ve müştereken d-amfetaminle etkileşmesini inceledik. Motor aktivite, periton içine d-amfetamin zerkinden 45 dakika sonra 10 dakika süreyle Y labirentinde ölçüldü. d-Amfetamin doza bağlı olarak motor aktiviteyi arttırdı. Spontan motor aktivite, 0.5,
1 ve 1.55 mg/kg d-amfetamin injeksiyonlarından sonra sırayla, kontrol cevap olan 4.5x0.5 den 14.772.6,42.6F4.2 ve 54.175.8 e yükseldi. Yalanma ve koklama gibi stere otipik davranışlar 2.5 mg/kg damfetaminle görülmeye başladı. Bu hareketler lokomotor aktiviteyi maskelediği için bu dozda lokomotor aktivitede azalma oldu (Şekil 1).
T gün süryle günde 50 mg/kg L-DOPA almış sıçanlarda 1 mg/kg amfetaminin motor aktiviteye olan etkisi kontrollerden düşüktü. (p < 0.05) (Şekil — 1,2). Denemeden 3 gün önce intracerebroventriküler olarak injekte edilen 250 ug 6-OHDA, i mg/kg d-amfetaminin sıçanlarda motor aktivite üzeriine olan etkisini arttırdı, Spontan motor aktivite 1 mg/kg d-amfetamin ile 37.5-7.5 dan 69.779.1 e yükseldi. (p < 0.01) bunun zıttı olarak 6-OHDA injeksiyonundan 30 gün sonra Il mg/kg d-amfetaminin yaptığı artış kontrollerden farklı değildi. Yedi gün süreyle günde 50 mg/kg L-DOPA almış sıçanlarda, yedinci gün intracerebroventriküler olarak 250 ug 6-OHDA verilmiş ve üç gün sonra 1 mg/kg amfelamin denendi. Bu sıçanlarda amfetamin cevabı kontrollerden farklı değildi (Şekil 3). Sonuçlar motor aktivite düzenlenmesinde merkezi monoaminerjik sistemin rölü ve ilaçların bu sisteme olan etkileri bakımından tartışıldı.

Keywords

Motor aktivite , 6-OHDA , L-DOPA

References

• Svensson, T., Waldeck, B. (1969). On the significance of central noradrenaline for motor activity: Experiments with a new dopamine beta hydroxylase inhibitor. European Journal of Pharmacology, 7, 278-282.
• Chan, O.-L., Webster, R. A. (1971). Importance of noradrenaline found in a functional pool in maintaining spontaneous locomotor activity in rats. British Journal of Pharmacology, 41, 700-708.
• Smith, C. B. (1963). Enhancement by reserpine and α-methyl dopa of the effects of d-amphetamine upon the locomotor activity of mice. Journal of Pharmacology and Experimental Therapeutics, 142, 343-350.
• Glowinski, J., Axelrod, J. (1965). Effect of drugs on the uptake, release and metabolism of 3H-norepinephrine in the rat brain. Journal of Pharmacology and Experimental Therapeutics, 149, 43-49.
• Carlson, A., Lindqvist, M., Dahlstrom, A., Fuxe, K., Masuoka, D. (1965). Effect on the amphetamine group on intraneuronal brain amines in vivo and in vitro. Journal of Pharmacology and Pharmacodynamics, 17, 521-524.
• Spencer, P. B. J., Turner, T. A. R. (1969). Blockade of biogenic amine synthesis: Its effect on the responses to leptazol and dexamphetamine in rats. British Journal of Pharmacology, 37, 94-103.
• Svensson, T., Waldeck, B. (1970). On the role of brain catecholamines in motor activity: Experiments with inhibitors of synthesis and of monoamine oxidase. Psychopharmacologia, 18, 357-365.
• Porter, C. C., Totaro, J. A., Stone, C. A. (1963). Effect of 6-hydroxydopamine and some other compounds on the concentration of norepinephrine in the hearts of mice. Journal of Pharmacology and Experimental Therapeutics, 140, 303-316.
• Tranzer, J. P., Thoenen, H. (1968). An electron microscopic study of selective acute degeneration of sympathetic nerve terminals after the administration of 6-hydroxydopamine. Experientia, 24, 155-156.
• Thoenen, H., Tranzer, J. P. (1968). Chemical synpathectomy by selective destruction of adrenergic nerve ending with 6-hydroxydopamine. Naunyn-Schmiedeberg's Archives of Pharmacology, 261, 211-288.
• Malmfors, T., Sachs, C. (1968). Degeneration of adrenergic nerves produced by 6-hydroxydopamine. European Journal of Pharmacology, 8, 81-92.
• Ungerstedt, U. (1968). 6-hydroxydopamine induced degeneration of central monoamine neurons. European Journal of Pharmacology, 56, 107-110.
• Burkard, W. P., Jalfre, M., Blum, J. (1969). Effect of 6-hydroxydopamine on behaviour and cerebral amine content in rats. Experientia, 25, 1295-1296.
• Evets, K. D., Iversen, L. L. (1970). Effects of protriptyline on the depletion of catecholamines induced by 6-hydroxydopamine in the brain of the rat. Journal of Pharmacology and Pharmacodynamics, 19, 525-532.
• Uretsky, N. J., Iversen, L. L. (1970). Effects of 6-hydroxydopamine on catecholamine containing neurones in the rat brain. Journal of Neurochemistry, 17, 269-278.
• Brese, G. R., Traylor, T. D. (1971). Depletion of brain noradrenaline and dopamine by 6-hydroxydopamine. British Journal of Pharmacology, 42, 88-99.
• Brese, G. R., Traylor, T. D. (1970). Effect of 6-hydroxydopamine on brain norepinephrine and dopamine: Evidence for selective degeneration of catecholamine neurons. Journal of Pharmacology and Experimental Therapeutics, 174, 413-420.
• Bartholini, G., Richards, J. G., Pletscher, A. (1970). Dissociation between biochemical and ultrastructural effects of 6-hydroxydopamine in rat brain. Experientia, 26, 142-144.
• Thoenen, H., Mueller, R. A., Axelrod, J. (1969). Trans-synaptic induction of adrenal tyrosine hydroxylase. Journal of Pharmacology and Experimental Therapeutics, 169, 249-254.
• Glowinski, J. (1970). Effects of amphetamine on various aspects of catecholamine metabolism in the central nervous system of the rat. In: Costa, E. & Garattini, S. (Eds.), Amphetamines and Related Compounds (pp. 301). Raven Press, New York.
• Carlsson, A. (1970). Amphetamine and brain catecholamines. In: Costa, E. & Garattini, S. (Eds.), Amphetamines and Related Compounds (pp. 289). Raven Press, New York.
• Randrup, A., Munkvad, I. (1967). Stereotyped activities produced by amphetamine in several animal species and man. Psychopharmacologia, 11, 800-810.
• Del Rio, J., Fuentes, J. A. (1969). Studies on the antagonism of stereotyped behaviour induced by amphetamine. European Journal of Pharmacology, 8, 73-78.
• Lemberger, L., With, I. D., Davis, J. M., Kopin, I. J. (1970). The effects of haloperidol and chlorpromazine on amphetamine stereotype behavior in the rat. Journal of Pharmacology and Experimental Therapeutics, 174, 428-433.
• D’Encarnacao, P. S., Dencarnacao, P., Tapp, J. T. (1969). Potentiation of amphetamine induced psychomotor activity by diethyldithiocarbamate. Archives Internationales de Pharmacodynamie, 182, 186-189.
• Botssier, J. R., Simon, P. (1966). De la potentialisation des effects de la DOPA par les inhibiteurs de la monoamine oxydase. Psychopharmacologia (Berlin), 8, 428-436.
• Butcher, L. L. (1969). Peripheral factors in the mediation of the effects of L-DOPA on locomotor activity. Journal of Pharmacology and Pharmacodynamics, 21, 614-616.
• Bartholini, G., Blum, J. E., Pletscher, A. (1969). Dopa-induced locomotor stimulation after inhibition of extracerebral decarboxylase. Journal of Pharmacology and Pharmacodynamics, 21, 297-301.
• Strömberg, U. (1970). DOPA effects on motility in mice: Potentiation by MK 485 and Dexchlorpheniramine. Psychopharmacologia, 18, 58-67.
• Evetts, K. D., Uretsky, N. J., Iversen, L. L., Iversen, S. D. (1970). Effects of 6-hydroxydopamine on CNS catecholamines, spontaneous motor activity and amphetamine induced hyperactivity in rats. Nature, 225, 961-962.
• Tulunay, C. F., Kiran, B. K., Kaymakçalan, Ş. (Year unknown). 6-hidroksidopamin'in sıçanda morfin abstinens sendromuna etkisi. (T.B.T.A.K TII, Bilim Kong. Tebliği).
• Ayhan, İ. H. (Year unknown). Morfin analjezisi ve morfine toleranslı sıçanların abstinens sendromu üzerine 6-hidroksidopamin'in etkileri. (İhtisas tezi).