Advertisement

Psychopharmacology

, Volume 78, Issue 3, pp 271–276 | Cite as

Role of dopaminergic neurotransmission in locomotor stimulation by dexamphetamine and ethanol

  • Ulf H. Strömbom
  • Bengt Liedman
Original Investigations

Abstract

Locomotor activity and brain tyrosine hydroxylation rate in vivo, assessed as dopa formation following dopa-decarboxylase inhibition by NSD 1015, was studied in mice. Dexamphetamine 91 mg/kg IP) induced increases in locomotor activity even from the high control baseline activity during the first 5 min in a motility meter. Inhibition of catecholamine synthesis by α-methyl-p-tyrosine (250 mg/kg) alone, given 30 min before test, reduced this high baseline locomotor activity, but such pretreatment did not affect the amphetamine-induced locomotor increase. The inhibition of synthesis itself was slightly attenuated by amphetamine. Low doses of apomorphine (0.1 and 0.2 mg/kg) markedly antagonized the initial locomotor increase by amphetamine but only incompletely antagonized the amphetamine-induced stimulation 15–30 min after the start of the recording. After reserpine pretreatment, apomorphine did not antagonize the amphetamine-induced locomotor stimulation. The data suggest that the release of transmitter causing behavioural stimulation by amphetamine is brought about via two independent mechanisms: facilitation of release from intact granular stores which is not critically dependent on continued catecholamine synthesis but is sensitive to receptor-mediated regulation, and facilitation of the release of newly synthesized transmitter, insensitive to such regulation. Results with ethanol suggest greater dependence on intact dopamine (DA) neurotransmission for the stimulatory effect of this drug. Dexamphetamine (4 mg/kg) caused a greater increase in striatal than in mesolimbic dopa formation, and apomorphine (0.2 mg/kg) only incompletely antagonized the effect in the former region. It is suggested that this difference reflects a relatively greater component of extrinsic feedback regulation of nigrostriatal neurones, the operation of which may contribute to a more pronounced increase in tyrosine hydroxylation, less sensitive to inhibition by apomorphine than that occurring in the mesolimbic nerve endings.

Key words

Amphetamine Ethanol Apomorphine Dopamine synthesis Receptors Locomotor activity Rats 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aghajanian GK, Bunney BS (1974) Pre- and postsynaptic feedback mechanisms in central dopaminergic neurons. In: Seeman P, Brown GM (eds) Frontiers in neurology and neuroscience research. The University of Toronto Press, Chapter 2Google Scholar
  2. Ahlenius S (1974) Neurochemical control of behaviour. Thesis, Göteborg (Gotab)Google Scholar
  3. Andén NE, Atack CV, Svensson TH (1973) Release of dopamine from central noradrenaline and dopamine nerves induced by a dopamine-β-hydroxylase inhibitor. J Neuronal Transm 34:93–100Google Scholar
  4. Atack CV, Magnusson T (1970) 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 solvent mixtures. J Pharm Pharmacol 22: 625–627Google Scholar
  5. Bunney BS, Aghajanian GH (1978) d-Amphetamine-induced depression of central dopamine neurons: Evidence for mediation by both autoreceptors and a striato-nigral feedback pathway. Naunyn-Schmiedeberg's Arch Pharmacol 304:255–261Google Scholar
  6. Bunney BS, Aghajanian GK, Roth RH (1973a) Comparison of effects of l-dopa, amphetamine and apomorphine on firing rate of rat dopaminergic neurones. Nature 245:123–125Google Scholar
  7. Bunney BS, Walters JR, Roth RH, Aghajanian GK (1973b) Dopaminergic neurons: Effect of antipsychotic drugs and amphetamine on single cell activity. J Pharmacol Exp Ther 185:560–571Google Scholar
  8. Carenzi A, Guidotti A, Revuelta A, Costa E (1975) Molecular mechanisms in the action of morphine and viminol (R2) on rat striatum. J Pharmacol Exp Ther 194:311–319Google Scholar
  9. Carlsson A (1966) Drugs which block the storage of 5-hydroxytryptamine and related amines. In: Eichler O, Farah A, Erspamer V (eds) Handbook of experimental pharmacology, vol 19. Springer, Berlin Heidelberg New York, pp 529–592Google Scholar
  10. Carlsson A (1970) Amphetamine and brain catecholamines. In: Costa E, Garratini S (eds) Amphetamines and related compounds. Raven, New YorkGoogle Scholar
  11. Carlsson A (1975) Dopaminergic autoreceptors. In: Almgren O, Carlsson A, Engel J (eds) Chemical tools in catecholamine research, vol 2. North Holland/American Elsevier, AmsterdamGoogle Scholar
  12. Carlsson A, Engel J, Strömbom U, Svensson TH, Waldeck B (1974) Suppression by dopamine-agonists of the ethanol-induced stimulation of locomotor activity and brain dopamine synthesis. Naunyn-Schmiedeberg's Arch Pharmacol 283:117–128Google Scholar
  13. Carlsson A, Davis JN, Kehr W, Lindqvist M, Atack CV (1972a) Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedeberg's Arch Pharmacol 275: 153–168Google Scholar
  14. Carlsson A, Engel J, Svensson TH (1972b) Inhibition of ethanol-induced excitation in mice and rats by α-methyl-p-tyrosine. Psychopharmacologia 26:307–312Google Scholar
  15. Carlsson A, Kehr W, Lindqvist M, Magnusson T, Atack CV (1972c) Regulation of monoamine metabolism in the central nervous system. Pharmacological reviews 24, No 2Google Scholar
  16. Carlsson A, Lindqvist M (1973) Effet of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J Pharm Pharmacol 25:437–440Google Scholar
  17. Carlsson A, Lindqvist M, Fuxe K, Hamberger B (1966) The effect of (+)-amphetamine on various central and peripheral catecholamine-containing neurones. J Pharm Pharmacol 18:128–130Google Scholar
  18. Chiara GD, Porceddu WL, Vargiu L, Argiolas A, Gessa GL (1976) Evidence for dopamine receptors mediating sedation in the mouse brain. Nature 264:564–566Google Scholar
  19. Cofer CN, Appley MH (1964) Motivation: Theory and research. Wiley, London, pp 269–301Google Scholar
  20. Costa E, Gropetti A, Naimzada MK (1972) Effects of amphetamine on the turnover rate of brain catecholamines and motor activity. Br J Pharmacol 44:742–750Google Scholar
  21. Dalsass M, German DC, Kiser AS, Speciale S (1979) Effects of d-amphetamine on dopaminergic neurons in the ventral tegmental area of the rat. Neurosci Abstr 5:553Google Scholar
  22. Engberg G, Svensson TH (1979) Amphetamine-induced inhibition of central noradrenergic neurons: A pharmacological analysis. Life Sci 24:2245–2254Google Scholar
  23. Engel J, Strömbom U, Svensson TH, Waldeck B (1974) Suppression by α-methyl-tyrosine of ethanol-induced locomotor stimulation: Partial reversal by l-dopa. Psychopharmacologia 37:275–279Google Scholar
  24. Engström G, Svensson TH, Waldeck B (1974) Thyroxine and brain catecholamines: Increased transmitter synthesis and increased receptor sensitivity. Brain Res 77:471–483Google Scholar
  25. Farnebo LO (1971) Effect of d-amphetamine on spontaneous and stimulation-induced release of catecholamines. Acta Physiol Scand 371:45–52Google Scholar
  26. German DC, Dalsass M, Kiser RS (1980) Electrophysiological examination of the ventral tegmental (A 10) area in the rat. Brain Res 181: 191–197Google Scholar
  27. Jackson DM, Andén NE, Dahlström A (1975) A functional effect of dopamine in the nucleus accumbens and in some other dopaminerich parts of the rat brain. Psychopharmacolgia 45:139–149Google Scholar
  28. Kehr W (1974) Temporal changes in catecholamine synthesis in rat forebrain structures after axotomy. J Neural Transm 35:307–317Google Scholar
  29. Kehr W, Carlsson A, Lindqvist M (1972) A method for the determination of 3,4-dihydroxyphenylalanine (dopa) in brain. Naunyn-Schmiedeberg's Arch Pharmacol 274:273–280Google Scholar
  30. Kehr W, Spechenbach W, Zimmermann R (1976) Interaction of haloperidol and γ-butyrolactone with (+)-amphetamine-induced changes in monoamine synthesis and metabolism in rat brain. J Neural Transm 40:129–147Google Scholar
  31. Kelly PH, Seviour P, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesion of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522Google Scholar
  32. Krsiak M, Steinberg H, Stolerman SP (1970) Uses and limitation of photocell activity cages for assessing effects of drugs. Psychopharmacologia 17:258–274Google Scholar
  33. Kuczenski R (1977) Biphasic effects of amphetamine on striatal dopamine dynamics. Eur J Pharmacol 46:249–257Google Scholar
  34. Morgenroth VH, III, Walters JR, Roth RH (1976) Dopaminergic neurons: Alterations in the kinetic properties of tyrosine hydroxylase after cessation of impulse flow. Biochem Pharmacol 25:655–661Google Scholar
  35. Nowycky MC, Roth RH (1977) Presynaptic dopamine receptors. Development of supersensitivity following treatment with fluphenazine decanoate. Naunyn-Schmiedeberg's Arch Pharmacol 300:247–254Google Scholar
  36. Obianwų HO (1969) Possible functional differentiation between the stores from which adrenergic nerve stimulation, tyramine and amphetamine release noradrenaline. Acta Physiol Scand 75:92–101Google Scholar
  37. Papeschi R (1975) Behavioural and biochemical interaction between AMT and (+)-amphetamine: Relevance to the identification of the functional pool of brain catecholamines. Psychopharmacologia 45:21–28Google Scholar
  38. Randrup A, Munkvad I (1966) Role of catecholamines in the amphetamine excitatory response. Nature 211:540Google Scholar
  39. Roth RH, Walters JR, Morgenroth VH, III (1974) Effects of alterations in impulse flow on transmitter metabolism in central dopaminergic neurons. In: Usdin E (ed) Neuropsychopharmacology of monoamines and their regulatory enzymes. Raven, New York, pp 369–384Google Scholar
  40. Salamone JD, Neill DB, Lindsay WS, Kizzort B, Justice JB (1980) Multiple site monitoring of dopamine release in freely moving rats. Abstr No 245:19. Society for neuroscience, Annual Meeting, CincinnattiGoogle Scholar
  41. Skirboll LR, Grace AA, Bunney BS (1979) Dopamine auto- and post-synaptic receptors: Electrophysiological evidence for differential sensitivity to dopamine agonists. Science 206:80–82Google Scholar
  42. Strömbom U (1976a) Catecholamine receptor agonists: Effects on motor activity and rate of tyrosine hydroxylation in mouse brain. Naunyn-Schmiedeberg's Arch Pharmacol 292:167–196Google Scholar
  43. Strömbom U (1976b) On the functional role of pre- and postsynaptic catecholamine receptors in brain. Thesis, Gothenburg 1975. Acta Physiol Scand Suppl 431Google Scholar
  44. Strömbom U (1977) Antagonism by haloperidol of the locomotor suppression induced by small doses of apomorphine. J Neural Transm 40:101–104Google Scholar
  45. Strömbom U, Svensson TH (1978) Antagonism of morphine-induced central stimulation in mice by small doses of catecholamine-receptor agonists. J Neural Transm 42:169–179Google Scholar
  46. Strömbom U, Svensson TH, Carlsson A (1977) Antagonism of ethanol's central stimulation in mice by small doses of catecholamine-receptor agonists. Psychopharmacology 51:293–299Google Scholar
  47. Svensson TH (1970) The effect of inhibition of catecholamine synthesis on dexamphetamine-induced central stimulation. Eur J Pharmacol 12:161–166. Erratum 13:139–140Google Scholar
  48. Svensson TH, Waldeck B (1970) On the relation between motor activity and the degree of enzyme inhibiton following inhibition of tyrosine hydroxylase. Acta Pharmacol et Toxicol 29:60–64Google Scholar
  49. von Voigtlander PF, Moore KE (1973) Involvement of nigro-striatal neurons in the in vivo release of dopamine by amphetamine, amantadine and tyramine. J Pharmacol Exp Ther 184:542–552Google Scholar
  50. Wang RY (1980) Dopaminergic neurons in the rat ventral tegmental area: Electrophysiological evidence for autoregulation. Abstr No 88:3, Society for Neuroscience, Annual Meeting, Cincinnatti, OhioGoogle Scholar
  51. Weissman A, Koe BK, Tenen S (1966) Antiamphetamine effects of following inhibition of tyrosine hydroxylase. J Pharmacol Exp Ther 151: 339–352Google Scholar
  52. Widerlöf E, Lewander T (1978) The relationship between amphetamine antagonism and depletion of brain catecholamines by alpha-methyl-p-tyrosine in rats. Naunyn-Schmiedeberg's Arch Pharmacol 304: 125–134Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Ulf H. Strömbom
    • 1
  • Bengt Liedman
    • 1
  1. 1.Dept. of PharmacologyUniversity of GöteborgGöteborgSweden

Personalised recommendations