IMPACT OF PERINATAL LITHIUM TREATMENT ON ANXIETY ANO DEPRESSION IN ADULT RATS
Keywords:
lithium, perinatal treatment, behavior, ratsAbstract
Introduction
Lithium salts (Li+) are used for the prophylactic treatment of bipolar disorder. Sometimes it is necessary to continue treatment even during pregnancy, as the risk of maternal morbidity is high.
Objective
To evaluate the impact of perinatal exposure to lithium at a prophylactic level. The susceptibility of female rat offspring to the development of anxiety and depression was verified in adulthood.
Methods
Wistar females drank 10mMol lithium chloride or 10mMol sodium chloride, ad libitum, as the only source of drink, in the pre- and/or post-natal (lactation) periods. After birth, the puppies underwent cross-fostering to form the four experimental groups (n=10 litters each) a) Control - saline during the pre- and post-natal periods; b) LiPos - Li+ during the postnatal period; c) LiPre - Li+ during the prenatal period and d) Li - Li+ during the pre and postnatal periods.
Results
No changes were observed in locomotor activity and behaviors associated with anxiety in the elevated plus maze test (Anova and Student-Newman-Keuls test, p>0.05). Lithium treatment also did not cause significant differences in escape latency in helpless rats (Anova and Student-Newman-Keuls, p>0.05).
Conclusion
The results suggest that perinatal lithium treatment does not alter the intensity of behavioral depression and anxiety induced in adulthood.
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References
Janicak PG, Watanabe MD. Estabilizadores do Humor. ln: Marcolin MA, editor. Interações farmacológicas com drogas psiquiátricas. Rio de Janeiro: Medsi; 1998. p.109-27.
Stahl SM. Psicofarmacologia: bases neurocientíficas e aplicações clínicas. Rio de Janeiro: Medsi; 1998.
lqbal MM, Gundlapalli SP, Ryan WG, Ryals T, Passman TE. Effects of antimanic moodstabilizing drugs on fetuses, neonates, and nursing infants. South Med J 2001; 94(3):304-22.
Llewellyn A, Stowe ZN Strader JR. The use of lithium and management of women with bipolar disorder during pregnancy and lactation. J Clin Psychiatry 1998; 59 (Suppl 6):57-64 discussion 65.
Silva VA, Moraes-Santos AR, Carvalho MS, Martins ML, Teixeira NA. Prenatal and postnatal depression among low incarne Brazilian women. Braz J Med Biai Res 1998; 31(6):799-804.
Edmonds LD, Oakley GP. Ebstein's anomaly and maternal lithium exposure during pregnancy. Teratology 1990; 41:551-2.
Jacobson SJ, Jones K, Johnson K, Ceolin L, Kaur P, Sahn D, et ai. Prospective multicenter study of pregnancy outcome after lithium exposure during first trimester. Lancet 1992; 339:530-3.
Zalstein E, Xoren G, Einarson T, Freedom RM. A case-contrai study on the association between first trimester exposure to lithium and Ebstein's anomaly. Am J Cardiol 1990; 65:817-8.
Vorhees CV, Brunner RL, Butcher RE. Psychotropic drugs as behavioural teratogens. Science 1979; 205:1220-5.
Lewis PJ. Efectos adversos de las drogas sobre el feto. ln: Lewis PJ, editor. Farmacología clínica en obstetrícia. Buenos Aires: Editorial Médico-Panamericana; 1985. p.27-35.
Dobbing J, Sands J. Annotation on comparative aspects of the brain grovvth-spurt. Early Hum Dev 1979; 3:79-83.
Rodier PM. Chronology of neuron development: animal studies and their clinicai implications. Dev Med Child Neural 1980; 22: 525-45.
Weinstock M. Alterations induced by gestational stress in brain morphology and behaviour ofthe offspring. Prog Neurobiol 2001; 65(5):427-51
Sechzer JA, Lieberman KW, Alexander GJ, Weidman D, Stokes PE. Aberranting parenting and delayed offspring development in rats exposed to lithium. Biai Psychiatry 1986; 21 (13): 1258-66.
Glockner R, Schwarz S, Jahne F. Enhanced effect of chronic stress on pregnancy outcome in Uje: Wist rats by prenatal treatment with lithium. Exp Toxic Pathol 1993; 45:35-7.
Glockner R, Karge E. lnfluence of chronic stress before and/or during gestation on pregnancy outcome of young and old Uje:WIST rats. J Exp Anim Sei 1991 ;4:93-8.
T eixeira NA, Lopes RCM, Secoli SR. Developmental toxicity of lithium treatment at prophylactic leveis. Braz J Med Biai Res 1995; 28(2):230-9.
Maj M, Pirozi R, Kemali D. Long term outcome of lithium prophylaxis in bipolar patients. Arch Gen Psychiatry 1991; 44:358-60.
Faria MS, Teixeira NA. Reversai of learned helplessness by chronic lithium treatment at a prophylactic levei. Braz J Med Biai Res 1993; 26:1201-12.
Teixeira NA, Pereira DG, Hermini AH. Chronic but not acute Li+ treatment prevents behavioral depression in rats. Braz J Med Biol Res 1995; 28:1003-7.
Guilherme MCG, Varriano AA, Teixeira NA. Influência do tratamento perinatal com salina sobre a aprendizagem e memória na prole de ratas. ln: Resumos [CD-ROM] da 18° Reunião Anual da Federação de Sociedades de Biologia Experimental, Curitiba, 2003. (Resumo 01.06.076:84)
Secoli SR, Teixeira NA. Chronic prenatal stress affects development and behavior depression in rats. Stress 1998; 2(4):273-80.
Pellow S, Chopin P, File SE Briley M. Validation of open: closed arm entries in an elevated plusmaze as a measure of anxiety in the rat. J Neurosci Methods 1985; 14:149-67.
Hermini AH, Teixeira NA, Mendes VE, Pereira DG. Development of a software to contrai depression experiments through "T he Learned Helplessness Model" 39a (part 1 ):430. ln: World Congress on Medical Physics and Biomedical Engineering. Rio de Janeiro; 1994.
Teixeira NA, Karniol IG. Dissociation of toxic and behavioral effects of lithium on rats. Braz J Med Biai Res 1985; 18(3):349-54.
EI-Messiha FS. Maternally-mediated developmental lithium toxicity in the mouse. Gen Pharmac 1993; 24(1 ):9-15.
Teixeira NA, Karniol IG. The influence of age and sex on weight variation in rats treated chronically with lithium chloride. Acta Pharmacol Toxicol 1982; 51:1-5.
Kersten L. Toxicity and renal elimination of lithium in rats of different ages. Arch Toxic 1991; 47: 135-44;.
Varriano AA, Guilherme MCG, Silva VA, Teixeira NA. Influência do tratamento perinatal com salina sobre modelos de doenças mentais em ratas. ln: Resumos [CD-ROM] da 18º Reunião Anual da Federação de Sociedades de Biologia Experimental, Curitiba; 2003. (Resumo 01.06.075:84).
Abbey H, Howard E. Statistical procedure in developmental studies species with multiplication offspring. Dev Psychobiol 1973; 6(4):329-35
Alonso SJ, Navarro E, Rodrigues M. Permanent dopaminergic alterations in the n.accumbens after prenatal stress. Pharmacol Biachem Behav 1994; 49(2):353-8.
Alonso SJ, Castellano MA, Afonso D, Rodríguez M. Sex differences in behavioral despair: relationships between behavioral despair and open fiel d activity. Physiol Behav 1991; 49(1 ): 69-72.
Poltyrev T, Keshet GI, Kay G, Weinstock M. Role of experimen tal conditions in determining differences in exploratory behavior of prenatally stressed rats. Dev Psychobiol 1996; 29(5): 453-62.
Guilherme MCG, Varriano AA, Silva VA, Teixeira NA. Efeitos do tratamento perinatal com lítio na memória e aprendizado de ratos. Rev Ciênc Méd, submetido em abril 2003.
Pellow S, File SE. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biachem Behav 1986; 17:721-25.
Hogg S. A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol Biachem Behav 1996; 54: 21-30.
Overmeier JB, Seligman MEP. Effects of inescapable shock upons subsequent escape and avoidance responding. J Comp Physiol 1967; 63:28-33.
Willner P. Animal models of depression: an overview. Pharmacol Ther 1990; 45:425-55;.
Seligman MEP. Helplessness. On depression, development and death. San Francisco: W.H. Freeman; 1975.
