Journal of Neural Transmission

, Volume 103, Issue 7, pp 765–776 | Cite as

Adaptive changes in the rat dopaminergic transmission following repeated lithium administration

  • M. Dziedzicka-Wasylewska
  • M. Maćkowiak
  • K. Fijaτ
  • K. Wędzony
Basic Neurosciences and Genetics


In the present study the alterations in the contents of dopamine (DA) and metabolites, as well as in the levels of mRNA coding for DA receptor D2, were determined in the rat striatum (STR) and nucleus accumbens septi (NAS), in correlation with the duration of lithium administration. Single or subchronic (3 days) administration of lithium produced less consistent effects as far as the levels of DA and metabolites are concerned; however, following 7 or 14 days of lithium administration, the DA release from terminals was significantly attenuated and the effect was more pronounced in NAS. After the same time of treatment, the increase in the levels of mRNA coding for the D2 receptor was increased; this might be interpreted as an adaptive change to the decreased dopaminergic transmission following the prolonged administration of lithium.


Lithium dopamine striatum nucleus accumbens mRNA D2 rat 


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  1. Angulo JA, Corini H, Ledoux M, Schumacher M (1991) Regulation by dopaminergic neurotransmission of dopamine D2 mRNA and receptor levels in the striatum and nucleus accumbens of the rat. Mol Brain Res 11: 161–166Google Scholar
  2. Baptista T, Teneud L, Contreras Q, Burguera JL, Burguera M, Hernandez L (1993) Effects of acute and chronic lithium treatment on amphetamine-induced dopamine increase in the nucleus accumbens and prefrontal cortex in rats as studied by microdialysis. J Neural Transm [Gen Sect] 94: 75–89Google Scholar
  3. Bernard V, Le Moine C, Bloch B (1991) Striatal neurons express increased level of dopamine D2 receptor mRNA in response to haloperidol treatment: a quantitive in situ hybridization study. Neuroscience 45: 117–126Google Scholar
  4. Berggren U (1985) Effects of chronic lithium treatment on brain monoamine metabolism and amphetamine-induced locomotor stimulation in rats. J Neural Transm 64: 239–250Google Scholar
  5. Bliss EL, Ailion J (1970) The effect of lithium on brain neuroamines. Brain Res 24: 305–310Google Scholar
  6. Bloom FE, Baetge G, Deyo S, Ettenberg A, Koda L, Magistretti PJ, Shoemaker WJ, Staunton DA (1983) Chemical and physiological aspects of the action of lithium and antidepressant drugs. Neuropharmacology 22: 359–365Google Scholar
  7. Bowers MB, Rozitis A (1982) Dopamine metabolism and catalepsy after lithium and haloperidol. Eur J Pharmacol 78: 113–115Google Scholar
  8. Bunney WE, Garland BL (1983) Possible receptor effects of chronic lithium administration. Neuropharmacology 22: 367–372Google Scholar
  9. Bunney WE Jr, Brodie HKH, Murphy DL, Goodwin FK (1971) Studies of alpha-methyl-para-tyrosine, L-DOPA and L-tryptophan in depression and mania. Am J Psychiatry 127: 872–881Google Scholar
  10. Carli M, Anand-Srivastava MB, Molina-Holgado E, Dewar KM, Reader T (1994) Effects of chronic lithium treatments on central dopaminergic receptor systems: G proteins as a possible targets. Neurochem Int 24: 13–22Google Scholar
  11. Chen JF, Qin ZH, Szele F, Bai G, Weiss B (1991) Neuronal localization and modulation of the D2 dopamine receptor mRNA in brain of normal mice and mice lesioned with 6-hydroxydopamine. Neuropharmacology 30: 927–941Google Scholar
  12. Chen JF, Aloyo VJ, Weiss B (1993) Continuous treatment with the D2 dopamine receptor agonist quinpirole decreases D2 dopamine receptors, D2 dopamine receptor messenger RNA and proenkephalin messenger RNA, and increases mu opioid receptors in mouse striatum. Neuroscience 54: 669–680Google Scholar
  13. Coirini H, Schumacher M, Angulo J, McEwen B (1990) Increase in striatal dopamine D2 receptor mRNA after lesions or haloperidol treatment. Eur J Pharmacol 186: 369–371Google Scholar
  14. Corrodi H, Fuxe K, Schou M (1969) The effect of prolonged lithium administration on cerebral monoamine neurons in the rat. Life Sci 8: 643–651Google Scholar
  15. Dziedzicka-Wasylewska M, Rogoż R (1995) The effect of prolonged treatment with imipramine and electroconvulsive shock on the levels of endogenous enkephalins in the nucleus accumbens and the ventral tegmentum of the rat. J Neural Transm [Gen Sect] 102: 221–228Google Scholar
  16. Dziedzicka-Wasylewska M, Przewlocka B, Prezewlocki R (1995) The effect of prolonged lithium administration on the cAMP level in the rat striatum. Pol J Pharmacol 47: 115–120Google Scholar
  17. Friedman E, Gershon S (1973) Effect of lithium on brain dopamine. Nature 243: 520–521Google Scholar
  18. Garver DL, Davis JM (1979) Minireview: biogenic amine hypothesis of affective disorders. Life Sci 24: 383–394Google Scholar
  19. Gerfen C, Engber T, Mahan L, Susel Z, Chase T, Monsma F, Sibley D (1990) D1 and D2 dopamine receptor regulated gene expression of striatonigral and striatopallidal neurons. Science 250: 1429–1432Google Scholar
  20. Gerner RH, Post RMN, Bunney WE Jr (1976) A dopaminergic mechanism of mania. Am J Psychiatry 133: 1177–1180Google Scholar
  21. Gottberg E, Groudin I, Reader TA (1989) Acute effects of lithium on catecholamines, serotonin, and their major metabolites in discrete brain regions. J Neurosci Res 22: 338–345Google Scholar
  22. Ho AK, Loh HH, Cravevs F, Hitzemann RJ, Gershon S (1970) The effect of prolonged lithium treatment on the synthesis rate and turnover of monoamines in brain regions of rats. Eur J Pharmacol 10: 72–78Google Scholar
  23. Jaber M, Fournier MC, Bloch B (1992) Reserpine treatment stimulates enkephalin and D2 dopamine receptor gene expression in the rat striatum. Mol Brain Res 15: 189–194Google Scholar
  24. Jaber M, Tison F, Fournier MC, Bloch B (1994) Differential influence of haloperidol and sulpiride on dopamine receptors and peptide mRNA levels in the rat striatum and pituitary. Mol Brain Res 23: 14–20Google Scholar
  25. Li PP, Tam YK, Young LT, Warsh JJ (1991) Lithium decreases Gs, Gi-1 and Gi-2 α-subunit mRNA levels in rat cortex. Eur J Pharmacol 206: 165–166Google Scholar
  26. Lopez-Corcuera B, Gimenez C, Aragon C (1988) Change of synaptic membrane lipid composition and fluidity by chronic administration of lithium. Biochim Biophys Acta 939: 467–475Google Scholar
  27. Maj J (1986) Repeated treatment with antidepressant drugs: responses by brain dopamine receptors. In: Hippius H, Klerman GL, Matussek N (eds) New results in depression research. Springer, Berlin Heidelberg New York Tokyo, pp 90–98Google Scholar
  28. Mclntyre IM, Kuhn C, Demitriou S, Fucek FR, Stanley M (1983) Modulating role of lithium on dopamine turnover, prolactin release, and behavioral supersensitivity following haloperidol and reserpine. Psychopharmacology 81: 150–154Google Scholar
  29. Otero-Losada ME, Rubio MC (1985) Striatal dopamine and motor activity changes observed shortly after lithium administration. Naunyn Schmiedebergs Arch Pharmacol 330: 169–174Google Scholar
  30. Palkovits M, Brownstein MJ (1988) Maps and guide to microdissection of the rat brain. Elsevier, New York Amsterdam LondonGoogle Scholar
  31. Pert A, Rosenblatt JE, Sivit C, Pert CB, Bunney WE (1978) Long-term treatment with lithium prevents the development of dopamine receptor supersensitivity. Science 201: 171–173Google Scholar
  32. Pittman KJ, Jakubovic A, Fibiger HC (1984) The effects of chronic lithium on behavioral and biochemical indices of dopamine receptor supersensitivity in the rat. Psychopharmacology 82: 371–377Google Scholar
  33. Poitou P, Bohuon C (1975) catecholamine metabolism in the rat brain after short- and long-term lithium administration. J Neurochem 25: 535–537Google Scholar
  34. Post R (1989) Mood disorders: somatic treatment. In: Kaplan HI, Sadock BJ (eds) Comprehensive textbook of psychiatry. Williams and Wilkins, Baltimore, pp 913–931Google Scholar
  35. Pybus J, Bowers GN Jr (1970) Measurement of serum lithium by atomic absorption spectrometry. Clin Chem 16: 139–143Google Scholar
  36. Reches A, Jackson-Lewis V, Fahn S (1984) Chronic lithium administration has no effect on haloperidol-induced supersensitivity of pre- and postsynaptic dopamine receptors in rat brain. Brain Res 246: 172–177Google Scholar
  37. Roffler-Tarlov S, Sherman DF, Tergerdine P (1971) 3,4-Dihydroxyphenylacetic acid in the mouse striatum: a reflection of intra- and extraneuronal metabolism of dopamine? Br J Pharmacol 42: 343–351Google Scholar
  38. Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 122: 509–522Google Scholar
  39. Schubert J (1973) Effect of chronic lithium treatment on monoamine metabolism in rat brain. Psychopharmacology 32: 301–311Google Scholar
  40. Seeman P, Grigoriadis D (1987) Dopamine receptors in brain and periphery. Neurochem Int 1: 1–25Google Scholar
  41. Srivastava LK, Morency MA, Bajawa SB, Mishra RK (1990) Effect of haloperidol on expression of dopamine D2 receptor mRNAs in rat brain. J Mol Neurosci 2: 155–161Google Scholar
  42. Staunton DA, Magistretti PJ, Shoemaker WJ, Deyo SN, Bloom FE (1982) Effects of chronic lithium treatment on dopamine receptors in the rat corpus striatum. II. No effect on denervation or neuroleptic-induced supersensitivity. Brain Res 232: 401–412Google Scholar
  43. Wedzony K, Golembiowska K, Zazula M (1994) Differential effects of CGP 37849 and MK 801, competitive and noncompetitive NMDA antagonists, with respect to the modulation of sensorimotor gating and dopamine outflow in the prefrontal cortex in rats. Naunyn Schmiedebergs Arch Pharmacol 350: 555–562Google Scholar
  44. Westerink BHC (1985) Sequence and significance of dopamine metabolism in the rat brain. Neurochem Int 7: 221–227Google Scholar
  45. Wood PL, Altar CA (1988) Dopamine release in vivo from nigrostriatal, mesolimbic and mesocortical neurons: utility of 3-methoxytyramine measurements. Pharmacol Rev 40: 163–187Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • M. Dziedzicka-Wasylewska
    • 1
  • M. Maćkowiak
    • 1
  • K. Fijaτ
    • 1
  • K. Wędzony
    • 1
  1. 1.Institute of PharmacologyPolish Academy of SciencesKrakówPoland

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