Perinatal Lithium Treatment Effects On Learning And Memory In Rats
Keywords:
lithium, perinatal treatment, behavior, learning, memory, rats, pregnancyAbstract
Introduction
Lithium (Li•) is the most appropriate therapy for the prophylaxis of bipolar patients during pregnancy and the postpartum period. However, its impact on behavior in offspring has been little studied.
Objective
To evaluate possible changes in the cognitive development of female puppies after perinatal treatment with lithium in prophylactic doses.
Methods
Wistar rats were treated with LiCI or NaCI 10mM/L solution, ad libitum, as the sole source of drinking during pregnancy and lactation. After birth, cross-adoption of the puppies was applied, forming the experimental groups (10 litters each): 1) Control - saline during the pre- and post-natal periods; 2) LiPos - Li+ during the postnatal period; 3) Li Pré - Li• during the prenatal period; 4) Li - Li+ during the pre- and postnatal periods. The pups (one per litter) were subjected to the following learning and memory tests in adulthood: escape test (TF), signaled active avoidance (EAS) and passive avoidance (PE). The open field test (AC) was used to evaluate the exploratory activity.
Results
Significant differences were found only in the EP response in the Li group (Li=24.4% x Control=70.1%, Anova & Student - Newman-Keuls; **p<0.01).
Conclusion
The results suggest that exposure to lithium during development may have lasting effects on learning, such as acquisition and attention. Exposure during pregnancy and lactation was necessary to produce detectable effects in adult rats. Further studies are needed to investigate the neural circuits affected by perinatal exposure to lithium.
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References
Packer S. Family planning for women with bipolar disorder. Hosp Com Psychiatry 1992; 43(5):479-82.
Altshuler LL, Cohen L, Szuba MP, Burt VK, Gitlin M, Mintz J. Pharmacological Management of Psychiatric lllness During Pregnancy: Dilemmas and Guidelines. Am J Psychiatry 1996; 153: 592-606.
Schou M. Lithium treatment during pregnancy, delivery and lactation: an update [Review). J Clin Psychiatry 1990; 51(10):410-13.
Sechzer JA, Lieberman KW, Alexander GJ, Weidman D, Stokes PE. Aberrating parenting and delayed offspring development in rat's exposure to lithium. Biai Psychiatry 1986; 2113: 1258-66.
Teixeira NA, Lopes RCM, Secoli SR. Developmental toxicity of lithium treatment at prophylactic leveis. Braz J Med and Biol Res 1995; 282:230-39.
Varriano MA, Varriano AA, Datti F, Datti M, Antunes E, Teixeira NA. Evidence that behavioral depression does not influence airway cell influx in allergic rats. Mediators of lnflammation 2001; 10:229-32.
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.
Radwanska K, Nokolae E, Knapsk E, Kaczmarek L.Differential response of two subdivisions of lateral amygdala to aversive conditioning as revealed by c-Fos and P-ERK mapping. Neuroreport 2002; 13(17):2241-6.
Vnauber J, Muller WE. Anseculin improves passive avoidance learning of aged mice. Pharmacol Res 2003; 47(3):225-33.
Meisel RL, Dohanich GD, Ward 1. Effects of prenatal stress of avoidance acquisition on open field performance and lordotic behavior in male rats. Psysiol Behav 1979; 22:527-31.
Faria MS, Teixeira NA. Reversion of learned helplessness by chronic lithium treatment at a prophylactic levei. Braz J Med Biol Res 1993; 26:1201-12.
Bear MF, Connors BW, Paradiso MA. Neurociências: desvendando o sistema nervoso. Porto Alegre: Artmed; 2002.
Stahl SM. Psicofarmacologia. São Paulo: Medsi; 2002.
Kovacs P, Hernadi 1. lontophoresis of lithium antagonizes noradrenergic action on prefrontal neurons of rat. Brain Res 2002; 23(1 ): 150-6.
Kameda K, Miura J, Suzuki K, Kusumi 1, Tanaka T, Koyama T. Effects of lithium on dopamine D2 receptor expression in the rat brain striatum. J Neural Transm 2001; 108(3):321-34.
Cahill L, Mc gaugh JL, Weinberger NM. The neurobiology of learning and memory: some reminders to remember. Trends Neuroscience 2001; 24(10):578-81.
Brandão ML. Psicofisiologia. São Paulo: Atheneu; 2000.
Robinson GE, Stewart DE. Postpartum psychiatric disorders. CMAJ 1986; 134(1):31-7.
Beers MJ, Berkow R. Manual Merk. 17 .ed. São Paulo: Merk & Co; 2000.
Ernst CL, Goldberg JF. The reproductive safety profile of mood stabilizers, atypical ant psychotics and broad-spectrum psychotrop ics. J Clin Psychiatry 2002; 63(4):42-55.
