Summary
Lithium chloride was given to rats i.p. at single doses of 2 and 10 meq/kg, respectively. It produced a suppression of motor activity and an increase in the dopamine content of the striatum. The magnitude of these effects were dose- and time-dependent as well as transient in nature. After 60 min of injection, the higher dose (10 meq/kg) reduced motor activity by 67% and increased striatal dopamine content by 56% while the lower dose (2 meq/kg) reduced motor activity by 42% and elevated striatal dopamine by 36%. These effects vanished 24 h after administration regardless the dose employed.
None of the two doses of LiCl altered either dopamine biosynthesis in vivo (measured as the accumulation of a precursor of synthesis after decarboxylase inhibition), or the activity of tyrosine hydroxylase ex vivo under subsaturating conditons (i.e. enzyme activity in the tissues obtained from the animals post mortem).
An increased deamination of tyramine by mono-amineoxidase (MAO) was found in striatal homogenates after 60 min of the injection of 2 or 10 meq/kg of LiCl. This was due to a lowerK m for the substrate as revealed by kinetic studies. LiCl treatment did not change the proportion of MAO A∶B.
As neither dopamine synthesis was increased nor the activity of the catabolic enzyme MAO was reduced (but it was oppositely enhanced), the increment in striatal dopamine content might have likely resulted from a reduced release and/or an increased amine reuptake by the neurons. We postulate that the reduced motor activity observed shortly after injection of LiCl would be related to an interference with striatal dopaminergic neurotransmission.
Similar content being viewed by others
References
Ahluwalia P, Singhal RL (1980) Effect of low dose lithium administration and subsequent withdrawal on biogenic amines in rat brain. Br J Pharmacol 71:601–607
Bliss EL, Ailion J (1970) The effect of lithium upon brain neuroamines. Brain Res 24:305–310
Carlsson A, Kehr W, Lindquist M, Magnusson T, Atack CV (1972) Regulation of monoamine metabolism in the central nervous system. Pharmacol Rev 24:371–384
Colburn RW, Goodwin FK, Bunney WE, Davis JM (1967) Effect of lithium on the uptake of noradrenaline by synaptosomes. Nature (Lond) 215:1395–1397
Corrodi H, Fuxe K, Hokfelt T, Schou M (1967) The effect of lithium on cerebral monoamine neurons. Psychopharmacologia 11:345–353
Corrodi H, Fuxe K, Schou M (1969) The effect of prolonged lithium administration on cerebral monoamine neurons in the rat. Life Sci 8:643–651
Costall B, Naylor RJ (1974) Specific asymetric behaviour induced by the direct chemical stimulation of neostriatal dopaminergic mechanisms. Naunyn-Schmiedeberg's Arch Pharmacol 285: 83–98
Cox C, Harrison-Read PE, Steinberg K, Tomkiewics M (1971) Lithium attenuates drug-induced “manic” activity in rats. Nature 232:336–338
Friedman E, Gershon S (1973) Effect of lithium on brain dopamine. Nature (Lond) 243:520–521
Gallager DW, Pert A, Bunney WE (1978) Haloperidol-induced presynaptic dopamine supersensitivity is blocked by chronic lithium. Nature 273:309–312
Gerbino L, Oleshansky M, Gershon S (1978) Clinical use and mode of action of lithium. In: Lipton MA, DiMascio A, Killan KF (eds) Psychopharmacology. A generation of progress. Raven Press, New York, pp 1261–1275
Gershon S, Shopsin B (1973) Lithium. Plenum Press, New York
Greenspan K, Aronoff MS, Bogdanski DF (1970) Effects of lithium carbonate on turnover and metabolism of norepinephrine in the rat brain. Correlation to gross behavioral effect. Pharmacology 3:129–136
Harrison-Read PE (1980) Behavioral evidence for increased dopaminergic activity after long-term lithium pretreatment in rats. IRCS Med Sci 8:313
Hartley EJ, Seeman P (1983) Development of receptors for dopamine and noradrenaline in rat brain. Eur J Pharmacol 91:391–397
Hasan F, Leonard BE (1982) Changes in behavior and neurotransmitter metabolism in the rat following acute and chronic sulpiride administration. In: Ackenheil M, Matussek N (eds) Special aspects of psychopharmacology. Expansion Scientifique Française, Paris, pp 67–82
Hedner Th, Lundborg P (1982) Effect of gammahydroxybutyric acid on catecholamine synthesis and utilization in the developing rat brain. J Neural Trans 54:19–28
Katz RI, Kopin KJ (1969) Release of3H-norepinephrine and3H-serotonin evoked from brain slices by electric field stimulation. Calcium dependence and the effects of lithium and tetrodotoxin. Biochem Pharmacol 18:1935–1939
Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OH-dopamine lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507
Knapp S, Mandell AJ (1973) Short and long term lithium administration effects on the brain's serotonergic biosynthetic systems. Science (NY) 180:645–647
Kuriyama K, Kurihara E (1982) Correlation between rotational behaviours and neurochemical changes associated with damage of rat striatum: analysis using unilateral microinjection of kainic acid. Neurochem Internat 4:551–555
Lentzen H, Philippu A (1977) Uptake of tyramine into synaptic vesicles of the caudate nucleus. Naunyn-Schmiedeberg's Arch Pharmacol 300:25–30
Maggi A, Enna SJ (1980) Regional alterations in rat brain neurotransmitter systems following chronic lithium treatment. J Neurochem 34:888–892
Mannisto PT, Saarnivaara L (1972) Effect of lithium on the analgesis caused by morphine and two antidepressants in mice. Pharmacology 8:6329–6335
Matthaei H, Lentzen H, Philippu A (1976) Competition of some biogenic amines for uptake into synaptic vesicles of the striatum. Naunyn-Schmiedeberg's Arch Pharmacol 293:89–96
McCaman RE, McCaman MW, Hunt JM, Smith HS (1965) Microdetermination of monoamineoxidase and 5-hydroxytryptophan decarboxylase activities in neurons tissues. J Neurochem 12:15–23
Otero Losada ME, Rubio MC (1984) Acute effects of lithium chloride on noradrenergic neurons from rat cerebral cortex. Gen Pharmacol 15:31–35
Poitou P, Bohuon C (1975) Catecholamine metabolism in the rat brain after short and long term lithium administration. J Neurochem 25:535–537
Rastogi RB, Singhal RL (1977) Lithium: modification of behavioural activity and brain biogenic amines in developing hyperthyroid rats. J Pharmacol Exp Ther 201:92–102
Reinhard JE Jr, Roth RH (1982) Noradrenergic modulation of serotonin synthesis and metabolism. Inhibition by clonidine in vivo. J Pharmacol Exp Ther 221:541–546
Schildkraut JJ (1974) The effects of lithium ion on norepinephrine turnover and metabolism: basic and clinical studies. J Nerv Mental Dis 158:348–360
Schildkraut JJ, Logue MA, Dodge GA (1969) The effects of lithium salts on the turnover and metabolism of norepinephrine in rat brain. Psychopharmacologia 14:135–141
Schubert J (1973) Effect of chronic lithium treatment on monoamine metabolism in the rat brain. Psychopharmacologia (Berl) 32:301–311
Segal DS, Callaghan M, Mandell AJ (1975) Alterations in behaviour and catecholamine biosynthesis induced by lithium. Nature (Lond) 254:58–59
Smith DF, Smith HB (1973) The effect of prolonged lithium administration on activity reactivity and endurance in the rat. Psychopharmacologia (Berl) 30:83–88
Stern DN, Fieve RR, Neff NH, Costa E (1969) The effect of lithium chloride administration on brain and heart norepinephrine turnover rates. Psychopharmacologia 14:315–322
Stock G, Magnusson T, Andén N-E (1973) Increase in brain dopamine after axotomy or treatment with gammahydroxybutyric acid due to elimination of the nerve impulse flow. Naunyn-Schmiedeberg's Arch Pharmacol 278:347–361
U'Prichard DC, Steinberg H (1972) Selective effects of lithium on two forms of spontaneous activity. Br J Pharmacol 44:349–350
Walters JR, Roth RH, Aghajanian GK (1973) Dopaminergic neurons: similar biochemical and histochemical effects of gamma-hydroxybutyrate and acute lesions of the nigroneostriatal pathway. J Pharmacol Exp Ther 186:630–639
Waymire JC, Bjur R, Weiner N (1971) Assay of tyrosine hydroxylase by coupled decarboxylation of dopa formed from 1-14C-1-tyrosine. Anal Biochem 43:588–600
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Otero Losada, M.E., Rubio, M.C. Striatal dopamine and motor activity changes observed shortly after lithium administration. Naunyn-Schmiedeberg's Arch. Pharmacol. 330, 169–174 (1985). https://doi.org/10.1007/BF00572429
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00572429